Showing posts with label proteinfolding. Show all posts
Showing posts with label proteinfolding. Show all posts

Wednesday, April 19, 2023

protein origami and other metaphors

The April issue of C & I contains my feature on alpha fold, the AI that can predict all protein structures, and the irony of this happening at the time in history when we realise that structure isn't everything.

Protein origami

Chemistry & Industry Volume 87, Issue 4, April 2023, Pages 22-25

access via:

Wiley Online Library (paywalled PDF)

SCI (premium content, ie members only)

If you would like to reflect on the merits of the title "protein origami", my short essay review of the book Metaphors in the life sciences might help you with that:

Metaphorically speaking

Chemistry & Industry Volume 87, Issue 4, April 2023, Page 35

access via:

Wiley Online Library (paywalled PDF of the whole review section)

SCI (premium content, ie members only)

Although I've seen this kind of title above way too many articles on protein folding, I'm loving the mildly origami-inspired title font of the feature.

Monday, July 23, 2018

bottom-up biology at Birkbeck

Way back in 2001, when I was switching to full-time writing but wanted to keep some kind of connection with the world of academia, I used to trek to London twice a week to reside at the School of Crystallography, Birkbeck College, as a science writer in residence. That was an interesting experience while it lasted, and I got some good articles out of it, but as the railway connection got worse and more expensive over time, it wasn't really sustainable in the long run. (In 1999 I had even applied for a few London-based jobs thinking the railways situation can't get worse but it did!) Moreover, as Birkbeck set up a joint Institute of Structural Molecular Biology (ISMB) with UCL in 2003 and turbo-charged its research in this field, the space I used to have just disappeared.

The ISMB hosts an international symposium every other year, and as I was there when the first one happened, I enjoy the nostalgia trip of attending the latest instalments if and when I'm organised enough to make it happen. This year I was lucky and got there for both days of the symposium. I was rewarded with an amazing meeting that covered both the distinguished history of BBK structural biology (Rosalind Franklin, Aaron Klug, JD Bernal ... ) and its very exciting present. And I got another article out of it which is out now:

Building blocks for bottom-up biology

Current Biology Volume 28, Issue 14, 23 July 2018, Pages R761–R764

FREE access to full text and PDF download



The famously dilapidated pair of Georgian townhouses, 21 and 22 Torrington Square, where Rosalind Franklin worked for the last five years of her life, were later demolished and gave way to this, the Clore Management Centre, which is where the symposium was held (own photo).


PS and I got to test-ride the new rail line Oxford to Marylebone, with Chiltern Rail, which is indeed a bit better than what we had so far.

Monday, April 17, 2017

disorder turns 20

Open archives


Today I’ll exceptionally present a feature from the archives that was published in Chemistry World, not in Current Biology.

The occasion is that today is the 20th anniversary of one of my favourite and most impactful papers from my research career, even though it did not result from actual research I did.

What happened back in 1997 was that my friend and colleague Kevin Plaxco happened to know about a paper from molecular biologists coming out on a weird mechanism controlling the growth of the tail (flagella) that certain bacteria use to swim. The tail is a hollow tube, and while it is being built, a certain signalling protein escapes through the tunnel and is lost to the cell. When the tube is finished and closed, the protein accumulates in the cell and thereby signals that no more bricks are needed to extend the tunnel.

What Kevin noticed was an aspect that left the molecular biologist authors of the original paper gloriously uninterested – namely the fact that to carry out its biological signalling function this protein needed to be an unfolded, 1D thread, as opposed to a complex 3D structure as all functioning proteins were supposed to be according to the prevailing dogma that sequence determines structure determines function.

So Kevin told me about this and suggested to write a News & Views piece for Nature, which we did, and which came out 20 years ago today. At the time there were only two or three other examples of “intrinsically disordered” proteins that are functional while unstructured. Mostly the evidence relied on NMR spectroscopy, which invites the objection that maybe the researchers didn’t get the conditions quite right and maybe the protein would be more orderly if they did x instead of y.

The beauty of the system we discussed was that the biological function of the protein made it absolutely necessary to unfold, as it wouldn’t fit through the tube in its folded state.

Anyhow, this turned out to be the beginning of a whole new research field which grew quite impressively over the next years, so in 2010 I had the pleasure of attending a research conference at Barcelona that was all about intrinsically disordered proteins.

And summarising what I learned at this conference, I wrote a feature about the topic which appeared in 2011, and which is freely accessible:

Anarchy in the proteome
Chemistry World, August 2011, pp 42-45
FREE access to PDF file




screenshot of our 1997 News & Views (PDF - if you hit the paywall, try this)

Wednesday, September 07, 2016

a fond farewell

Rainer Jaenicke 1930-2016

My old professor or Doktorvater, as we like to call PhD supervisors in Germany once the title is in the bag, died at the end of July aged 85. Throughout our shared project (one year final year thesis plus three years doctoral thesis) he was a generous friend more than a boss, and remained one in the 23 years after. So, I’ll try to honour him with an obituary, which is not a format I have often had to write, but as time goes on, one does tend to have more farewells to make. Here’s my first attempt, I may add to it later.

Rainer Jaenicke was the youngest of the four children of a semi-famous chemist, Johannes Jaenicke (1888-1984), who during the Weimar Republic was the assistant of Nobel Laureate Fritz Haber, assisting, among other projects, with the doomed attempt to isolate gold from sea water to pay off Germany’s debt, and his wife Erna Buttermilch (1895-1961).

Johannes Jaenicke spent much of his long life meticulously compiling material for a biography of the great chemist and controversial figure (Haber’s ammonia synthesis process produces half the nitrogen contained in the bodies of the world population, but he also pioneered the use of chemical weapons), but, as he lost his eyesight with age, he ended up being unable to write it. All existing biographies of Haber are based on Johannes Jaenicke’s extensive collection, which has been archived by the Max Planck Society.

His three sons all became professors of some kind of chemistry. Walther Jaenicke (1921-2011) of physical chemistry at the University of Erlangen-Nürnberg; Lothar Jaenicke (1923-2015) of biochemistry at Cologne, and Rainer Jaenicke of biophysical chemistry at Regensburg.

The one thing I know about Rainer Jaenicke’s childhood in Frankfurt is that at age 13, he teamed up with a young pianist who accompanied his flute playing, Agathe Calvelli-Adorno. They lived happily ever after, as they say, and played music together for over 70 years.

Both families had partial Jewish background and suffered for it during the Nazi time, but made it through. Her Jewish grandmother was deported to concentration camp Theresienstadt and died soon after liberation. The Jaenicke brothers saw their career options limited by being fractionally Jewish according to the Nazi arithmetics (through their mother) but made up for it after the end of the “1000 years”.

Rainer Jaenicke married his pianist just before he obtained his PhD in physical chemistry with Hermann Hartmann (1914-1984) in Frankfurt, started a family, and got his Habilitation in 1963. With their children, they set off to Pittsburgh, Pennsylvania, where he worked with Max Lauffer (1914-2012) until 1969. Soon after his return he secured a professorship at the newly founded University of Regensburg, Bavaria. He took the chair for biophysical chemistry, which he held until his retirement in 1999. I believe he also served on the committee that commissioned / chose the around 30 major artworks that are scattered around the campus. For a project of this size it was a legal obligation to have a certain amount of “Kunst am Bau”, and there is a nice little book, called “Rund um die Kugel,” discussing all the artworks.

From the US, he brought back the research interest of protein assembly systems such as tobacco mosaic virus (TMV) – a classical system to study self-assembly which in my student days was still used in the practical biochemistry course in his department. From there, his research interests widened to protein folding and stability, including stability under extreme physical conditions like salinity, high and low temperatures and high pressures, which is where my thesis happened.

By the 1990s, one of his trademarks was to keep old-fashioned physical methods of analysis alive, especially analytical ultracentrifugation. This method involves spinning a sample so fast (40,000 rpm would be a typical speed) that large molecules such as proteins are gradually pulled out of solution by the centrifugal force. And this happens in a transparent cell, such that one can shine light through the sample and actually watch the molecules go down.

During my time in the lab (1989-1993) he kept two Beckman model E centrifuges alive and spinning, which was an achievement in itself, as the company had stopped making and indeed servicing these instruments, each the size of a generously-proportioned wardrobe, some time in the 1980s. Several dead machines in the basement were cannibalised for spares. As he was reluctant to persuade students to dedicate three or four years of their lives to an extinct technology, he did many of the centrifugation runs himself, and had great fun fiddling around with the machines.

And right he was too, because around that time, Beckman changed their mind and decided to develop a new instrument from scratch. I vividly remember Howard Schachman (1918-2016 - he died a week after RJ) visiting the lab, another model E aficionado, recalling how the company asked him for advice. As they had closed down the relevant department many years ago and fired everybody who knew anything about analytical ultracentrifuges, they were facing an uphill struggle trying to build a new one. But they got there in the end, and the instruments are now a bit more compact, so they can sit on a lab bench and feed their results to a computer.

As a supervisor, he was very generous with ideas, suggestions and help in establishing collaboration opportunities. I had collaborations with five labs outside Regensburg, four of which he enabled with phone calls to the relevant group leaders (the fifth was someone I met at a conference). While always ready to offer this kind of help and support, he never ever told me what to do – I had a rather painful awakening when I moved on to a postdoctoral fellowship in the UK and lost some 95% of the freedom I had been used to.

Part of the reason for my freedom was in the fact that during my doctoral thesis I was the only person in the lab working on the effects of high hydrostatic pressure. There were crowds of protein folding people and of those doing thermal stability, a few looking at salinity. Thus, there was no need for higher level co-ordination, there was no risk of my work overlapping anybody else’s, and I could basically do whatever I wanted. In this situation, as my own sub-group leader, and as I was also writing my own papers from day one, I put the asterisk indicating the correspondence author behind my name, just on the naïve assumption that he wouldn’t want to be troubled with the paperwork. He never queried that – only when we wrote a review together after I left the lab did he regain the asterisk, which any other professor would have claimed as their statutory right throughout.

Incidentally, he didn’t try to steer his children into a certain direction either. His daughter became a nurse, his sons an actor and an artist. He always highlighted their career choices – very unusual for a family of chemists – with pride, contrasting them to the children of colleagues (presumably including, though not mentioning, his brother) who were groomed to follow in the scientific tradition.

During my Regensburg years, I gained the impression that he had never really adapted to the Bavarian temperament of the people around him. Regensburg being a modern university serving a regional constituency (as opposed to the ancient universities like Heidelberg which attract students from all of Germany and indeed abroad), even most of the faculty colleagues had a conspicuous regional accent - not just in their language but also in their thinking and (conservative) worldview. He probably found he had more in common with the many international visitors he invited to Regensburg than with his immediate colleagues and next-door neighbours.

Thus, even though regulations for professors of his generation would have enabled him to use university facilities as an emeritus indefinitely, it was no big surprise to hear that in the late 1990s, after retiring at 68, he moved to the small town of Schwalbach am Taunus, within S-Bahn commuting distance of the city of Frankfurt, which he routinely referred to as home. The couple bought a bungalow – modest looking on the ground floor, but with a basement doubling the area and providing an impressive exhibition space for works of their artist son, Alexander Calvelli, as well as other graphic works which they collected. There were also guest rooms complete with musical instruments – visitors had the choice of sleeping in the presence of a harpsichord or a grand piano.

For nearly two decades, they kept a busy social and musical life at Schwalbach. The last time I visited, in the spring of 2014, the onset of memory loss was noticeable, although he could still play music. His condition gradually worsened to cut him off from the outside world, with the impressions from music remaining the last connection.

some items from my collection of RJ memorabilia ...

Thursday, October 16, 2014

useful anarchy

Intrinsic disorder in proteins has fascinated me ever since 1997, when Kevin Plaxco asked me to co-author a News & Views piece (1) on what was then an emerging topic. By now it is an established scientific phenomenon feeding a whole research community, so I even had the opportunity to attend a conference about it a few years ago, and write a feature for Chemistry World among other articles.

We now know that intrinsically disordered proteins play an important role in nature. Quite a few of them work in molecular recognition and can achieve specific binding by “folding around” their target. Others are medically relevant. For instance, there are disordered domains (an oxymoron for the protein folding crowd to chuckle or argue about) in virus proteins and in transcription factors that are important targets for cancer drugs.

If nature can find use for disordered sequences, maybe scientists can also use them in molecular design? Kevin’s group at the University of California at Santa Barbara has now demonstrated an intriguing approach in which disordered sequences (of DNA, this time) can make a receptor more cooperative, meaning more likely to bind a second molecule once it has bound the first (2). The best known natural example of molecular cooperativity is the binding of oxygen to haemoglobin in our red blood cells – it can carry up to four molecules, and each position filled increases the affinity of the remaining ones. The attraction, for haemoglobin as for biotechnologists, is that cooperative binding has a much sharper transition, switching from all empty to all full in a narrower range of concentrations than a non-cooperative receptor would.

But how do you force a receptor to be cooperative if it isn’t naturally inclined to do this? What first author Anna Simon and colleagues in the Plaxco lab did was to cut the receptor (a DNA aptamer in this work, but it should in principle be possible with proteins as well) in two halves, then duplicate each half. If you think of a complete working receptor as a pair of robotic hands that can grab a ball, they glued two left hands together and two right hands, but a connected pair of left and right was needed to carry out the desired function. They then connected the ends of the left and right construct with a DNA sequence that prefers to be disordered.

Bringing one pair of robot hands together to grab one ball comes at a cost, as the disordered DNA linker loses entropy (i.e. opportunities to adopt many random conformations) when its two ends are brought closely together. Once the first ball is firmly grabbed, however, and this entropic fee has been paid, the second pair of hands is suitably arranged in close proximity and ready to grab the second ball without having to pay any entropic costs for that. Thus, as in haemoglobin, the second binding event is much more favourable than the first.

Image: Anna Simon / ref. (2)

Simon et al. tried this out with three different DNA receptors, from a primitive one binding mercury ions to a sophisticated aptamers for the molecules cocaine and doxorubicin, and found that all showed some cooperativity, and one receptor, the one for doxorubicine, gave results within the error margins of the values that theory predicts for perfect cooperativity.

Seeing this works with all three DNA receptors tested, it should also work with others and could also be transferred to proteins. In fact, a recent paper suggests that nature also uses this trick in proteins already (3). Then it could be expanded to more than two binding sites, and it would be good to have high-resolution structures of these constructs to analyse their function in detail. The application of disorder in molecular engineering may be a whole new research field that has just been born.

references

(1) K. W. Plaxco and M. Groß, Nature 1997, 386, 657.
(2) A. J. Simon et al, Proc. Natl. Acad. Sci. USA 2014, DOI: 10.1073/pnas.1410796111
(3) A. C. Ferreon et al., Nature 2013, 498, 390.

Friday, June 06, 2014

archaic proteins and all that Bach

In the round-up of German pieces published in May-June 2014 we have medical marijuana, curious carbohydrates, and paleo proteins, as well as intellectual giants from Johann Sebastian Bach to Dr House.

Wirkstoff THC: Marihuana-Medizin macht Ernst
Chemie in unserer Zeit Vol 48, No 3, p 163

Biochemie: Kohlenhydrate spielen Protein
Chemie in unserer Zeit Vol 48, No 3, p 167

Ausgeforscht: Kobalt im Blut
Nachrichten aus der Chemie Vol 62, No 5, p 595

Ausgeforscht: Proteinreiche Buchstabensuppe
Nachrichten aus der Chemie Vol 62, No 6, p 727

Blickpunkt Bio: Proteine aus der Urzeit des Lebens
Nachrichten aus der Chemie Vol 62, No 6, pp 632-634

Oh, and I nearly forgot, the paleo proteins made the cover of Nachrichten:

Tuesday, April 08, 2014

sense and sensitivity

I've been following the work of Kevin Plaxco's lab on biosensors made from DNA aptamers since the beginnings, and last November there was a new breakthrough to report, the development of a sensor that can monitor the concentration of a target substance in real blood in real time.

I've taken this as an opportunity to write a feature on real time sensors which has now come out:

Biosensors in real time Chemistry & Industry 2014, Nr 4, pp 42-45
restricted access (but drop me a line if you want a pdf file)

In the same issue, I also have a review of the book Bioactives in Fruit:

The good fruit guide Chemistry & Industry 2014, Nr 4, p 51
restricted access (but drop me a line if you want a pdf file)

which is a good excuse to embed one of my foodporn photos:

Friday, January 24, 2014

latest spin on carbohydrates

Even though I did much of my PhD thesis with the characteristic whining of two ancient, wardrobe-sized Beckman model E analytical ultracentrifuges in the background, I didn't really expect to get a chance to write something about this technique any time soon. It was widely used to study molecular weight and assembly of proteins back in the 1970s but for a time it became so unfashionable that there was no company left making or servicing the instruments, and only hardcore fans like my PhD supervisor, Rainer Jaenicke, kept the last of these dinosaurs alive.

By now, the technique has been rediscovered, new centrifuges have been developed and built, and various groups are using the technique. In an intriguing development, the groups of Steve Harding and Thomas Heinze have shown that certain carbohydrates can assemble reversibly just like oligomeric proteins. Read all about it in my news story which is out now in Chemistry World online, free access:

Self-assembling carbohydrates behave like proteins

Searching for an illustration for this article, I discovered this video of a simulation showing what happens to protein molecules in the cell of an ultracentrifuge. Simulation is of lysozyme in water, so nothing to do with carbohydrates, but I thought it's a lovely visualisation of the technique:

Source: Díez A, Ortega A, Garcia de la Tore J (2011). "Brownian dynamics simulation of analytical ultracentrifugation experiments". BMC Biophysics. DOI:10.1186/2046-1682-4-6.

via wikimedia commons.

Monday, December 09, 2013

dances with diatoms

German publications in November and December cover foaming proteins, dance your PhD, chemical elements you can by from Holland & Barrett, boron-boron triple bonds, and diatoms. Phew. I won't even try to conjure up a connection between these, apart from the byline. So here goes:

Tierischer Eischnee und andere Schäume
Nachrichten aus der Chemie 2013, 61, 1227-1229
(a feature in English covering the same ground is here)

Ausgeforscht: Elemente für den Hausgebrauch
Nachrichten aus der Chemie 2013, 61, 1307

Ausgeforscht: Tanze deine Diss
Nachrichten aus der Chemie 2013, 61, 1191

Kieselalgen: Weder Tier noch Pflanze, aber klimarelevant
Chemie in unserer Zeit 47, 368-374, DOI: 10.1002/ciuz.201300621
abstract and restricted access to PDF download

Dreifachbindungen: Bor-Chemie im Aufwind
Chemie in unserer Zeit 47, 340
abstract and restricted access to PDF download

Wednesday, November 20, 2013

foaming proteins

If you work with proteins in a lab, one thing is for sure: you do not want your protein solution to foam. When it does foam, you can probably throw it away. Unless, that is, it is one of the rare proteins that are meant to act as detergents. So far, they have only been discovered in tropical frogs and in the sweat of horses, so that's why my latest feature is called:

Only frogs and horses

Chemistry & Industry November 2013, pp 24 - 27

restricted access to full text

I'll be happy to send pdf reprints if you want one, email me at

m i c h a e l g r r aaaaatttt y a h o o ddoooottt co dddddooottt uk
(chew that, spammmmbots!)

Friday, August 23, 2013

sweaty horses

Just one article out in German this month, which is about the surfactant protein latherin from horse sweat:

Pferdeschweiß-Protein hält Forscher auf Trab

Chemie in unserer Zeit

Volume 47, Issue 4, page 208, August 2013

Abstract and restricted access to PDF file

An English version of this story appears here.

Tuesday, July 02, 2013

foam from the horse's mouth

In a late follow-up to the frog foam story from 2009, I covered the structure of an equine protein coming from the same groups. Latherin is found in the sweat and saliva of horses and has unusual surfactant properties suggesting a new mechanism.

Read all about it in Chemistry World (free access):

A foaming protein from the horse’s mouth

NB: this came out so quickly that I actually missed it when it appeared, hence the slight delay in horn-tooting.

horses & buttercups

Some not so sweaty horses salivating over buttercups in a field near our house.

Tuesday, March 19, 2013

how to design new enzymes

Scientists are now able to design new enzymes to catalyse reactions for which a natural enzyme doesn't exist. I've rounded up some of the first success stories in enzyme design for my latest feature which is out now:

Evolving new types of enzymes

Current Biology, Volume 23, Issue 6, R214-R217, 18 March 2013

doi:10.1016/j.cub.2013.02.054

Free access to

HTML text

PDF

Sunday, December 16, 2012

peptides, proteins and poo

the articles published in German this month cover innovative toilets, non-ribosomal peptides, and the story behind this year's chemistry Nobel (G-protein coupled receptors).

WC 8
Nachrichten aus der Chemie 60, 1175

Peptidsynthese ohne Ribosomen
Nachrichten aus der Chemie 60, 1198-1199

Enthüllungen aus dem Reich der Sinne
Spektrum der Wissenschaft Nr. 12, 24-27

PS Oh, there's also a book review in the special review section of the "in unserer Zeit" journals:

Kleine Nachhilfe: Antworten auf Kinderfragen (review of: Endlich Mitwisser, Holger Wormer and Michael Dietz)
Chemie in unserer Zeit 46, Nr 6, Treffpunkt Buch plus, V

Thursday, November 01, 2012

a special proteasome for the immune system

The round-up of German pieces in November has only one article, covering the crystal structure of the immunoproteasome:

Molekularmedizin: Recyclingtonne für das Immunsystem – genauer betrachtet

Vom zelleigenen Schredder für Proteine, Proteasom genannt, besitzen Immunzellen eine Sonderausfertigung. Jetzt haben Forscher dessen Aufbau im Detail untersucht. Damit hoffen sie, Medikamente gegen Autoimmunkrankheiten zu entwickeln.

Spektrum der Wissenschaft Nov. 2012, S. 20-22

beginning of the text and restricted access to full text

I've covered some aspects of this work in English earlier this year, in a feature about symmetry and complexity.

(image: © Prof. Michael Groll/Technische Universitaet München.)

Friday, June 01, 2012

roundup of German pieces

My articles published in German this month include one about protein structure prediction, one about flu viruses, and a tongue-in-cheek appreciation of kitchen experiments.

Spektrum der Wissenschaft Nr 6, S. 18-20
Proteinstrukturen vorhersagen – dank Verwandtschaftsbeziehungen

Die dreidimensionale Struktur eines Proteins ist durch die Abfolge der einzelnen Aminosäuren eindeutig festgelegt. Trotzdem fällt es Forschern immer noch schwer, sie zu berechnen. Vergleiche zwischen verwandten Eiweißstoffen können helfen.
beginning of the text and limited access to PDF file

Nachrichten aus der Chemie Bd. 60, Nr 6, S. 632
Experimentierkunst in der Küche

Nachrichten aus der Chemie Bd. 60, Nr 6, S. 654-655
Globale Grippegefahr

PS: nearly forgot:

Chemie in unserer Zeit 46, 134
Alzheimer-Demenz: Amyloid-Plaques - wie sie entstehen und wie man sie wieder los wird

Tuesday, May 22, 2012

amyloid and Alzheimer's disease

Back in the late 90s, I was working with some model peptides which I had designed for use in studies of nascent protein folding, but they kept aggregating. Chris Dobson suggested to check whether the aggregates had the hallmark featres of amyloid, and indeed they had, so I slipped into the study of amyloid, which is the kind of tangled protein aggregate one finds in Alzheimer's disease, BSE, and Parkinson's. Quite a few others did at the time, as many proteins and peptides had the ability to form these structures, even if their native states had no disease association whatsoever.

I haven't done much about amyloid since publishing my last research papers, but recently spotted a few papers that looked promising both for the understanding of amyloid formation and for the treatment of Alzheimer's disease, so I wrote a feature about these things, which is out in Current Biology today.

Understanding amyloid and Alzheimer's disease

Current Biology, Volume 22, Issue 10, R381-R384, 22 May 2012

doi:10.1016/j.cub.2012.05.006

html text

PDF file

(NB: my features remain on free access only until the next issue appears, i.e. normally 2 weeks, sometimes 3, and they return to free access a year after publication)

Alois Alzheimer (1864-1915)

(Wikipedia)

Friday, March 23, 2012

chaperone movies

Back in the 90s I did some research on the molecular chaperone GroEL, which at the time didn't even have a crystal structure to its name. It is a great pleasure to see that the accumulation of structural and functional knowledge on this protein has now reached the stage where researchers can assemble snapshots to a movie showing plausible twists and turns that the seen subunits of each ring may carry out during their functional cycle.

The paper from Helen Saibil and colleagues at Birkbeck College, London, appeared in Cell (online) yesterday (D K Clare et al, Cell, 2012, DOI: 10.1016/j.cell.2012.02.047) and I wrote a news item for Chemistry World which has gone live today:

Molecular chaperones caught on film.


PS (23.4.2012): a related paper that just came out in Biophys J. and is freely accessible: Prying Open Single GroES Ring Complexes by Force Reveals Cooperativity across Domains Akiko Ikeda-Kobayashi, Yukinori Taniguchi, David J. Brockwell, Emanuele Paci and Masaru Kawakami Biophysical Journal, Volume 102, Issue 8, 1961-1968, 18 April 2012 doi:10.1016/j.bpj.2012.03.046

Tuesday, March 20, 2012

symmetry and complexity

My latest feature in Current Biology deals with complexes built from several identical or different protein subunits. There are good reasons why nature likes to build highly symmetrical assemblies from identical protein units, but on the other hand there are also good reasons why such structures may diversify and evolve highly complex arrangements of different subunits, with the proteasome, shown below, being a case in point.


Symmetry and complexity in protein oligomers
Current Biology, Volume 22, Issue 6, R175-R177, 20 March 2012
doi:10.1016/j.cub.2012.03.001

summary page

PDF file

(NB: my features remain on free access only until the next issue appears, i.e. normally 2 weeks, sometimes 3, and they return to free access a year after publication)

(image: © Prof. Michael Groll/Technische Universitaet München.)

Tuesday, January 24, 2012

folding helpers

More than four decade have passed since protein folding was recognised as a "problem" inasmuch as nature can find the right conformation out of an astronomical number of possibilities in a split second using only the information contained in the sequence, while we mere mortals can look at the amino acid chain and have trouble to work out which bit goes where. During that time, a lot of effort has gone into clarifying some mechanistic principles, elucidating the role of helper proteins (molecular chaperones) in the cell, and creating algorithms that can predict structures of small proteins. For large proteins, however, folding prediction is still a hard problem.

I've written a feature covering some of the most original approaches that have in recent years been applied to the folding (prediction) problem, including the distributed computing network folding@home, the crowdsourcing project Foldit, and recent work on using the information included in evolutionary relatedness of protein families. The feature appears in Current Biology today and is freely accessible to all:

Folding research recruits unconventional help
Current Biology, Volume 22, Issue 2, R35-R38, 24 January 2012
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PS In other news, my previous feature, We need to talk about nitrogen, is currently in 8th position in the Current Biology download chart.