protein in the womb

Scientists at Birkbeck College, London, have obtained the first images of a new-born protein in the “womb” of an enclosure that helps it find the proper structure.

Most of our genes serve the production of different proteins, which first emerge as a long string of building blocks, the amino acids. This string has to arrange itself into a well-defined pattern of coils, twists, and turns, so the protein can proceed to fulfill its biological function in the cell. For this process, known as folding, many proteins need helper proteins known as molecular chaperones. An important group of these helpers comes in the shape of a molecular barrel, which accommodates the new-born protein and releases it when it has attained its properly folded structure.

As the newborn moves and wriggles around in this barrel, researchers have so far been unable to get a clear picture of it. The group of Helen Saibil at the department of crystallography, at London’s Birkbeck College, in collaboration with the group of Saskia van der Vies at the Free University, Amsterdam, has now succeeded in imaging such a “newborn protein in the womb” by using a particularly large protein baby. The researchers studied the case of a virus that infects bacteria (a bacteriophage) and uses the bacterial barrel to help fold its own shell protein. This protein is too large for the barrel, such that the virus brings its own lid along so its protein can be securely locked up in the folding chamber.

This hijacking by a virus is rather unfortunate and fatal for the bacterium concerned, but it is a lucky break for structural biologists, as the bulky virus protein can’t move around as much as other proteins do. In fact, its position inside the barrel was sufficiently well defined such that Saibil’s team succeeded in taking its picture using low temperature electron microscopy to image the proteins in their natural state, and computer image processing to distinguish between complexes captured at different stages of binding and assembly.

Comparing their images to the existing pictures of the empty barrel, the researchers could gain valuable insights into how a protein is bound and released during the assisted folding process. They could also observe that the enclosure, like a womb, has to stretch to accommodate this relatively large protein baby.

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This is a draft press release I wrote, regarding a paper that appeared in the current issue of Nature (1.1.), vol. 457, p. 107