The second in a series of biophysical questions.
Proteins are molecules. As is the case for every molecule, the constituent atoms and inter-atomic bonds determine the overall shape. In general, a small or stiff molecule has a well-defined form. In contrast, long, chain-like molecules as found in plastics or the gel-formers of the last post are typically floppy and amorphous. Proteins, however, are long, chain-like molecules that do adopt an exact structure, with each type of protein having its own particular three-dimensional form. There are exceptions — some proteins are naturally disordered, and some can switch between configurations — but in general a protein’s shape is a robust signifier of its identity.
Revealing the shapes of proteins was both a triumph of mid-twentieth-century biophysics and an unsolved, ongoing challenge. Decades ago, we learned to bounce X-rays off of protein crystals, revealing their structures in atomic detail. Not all proteins are amenable to this approach, however. New experimental techniques, for example using electron beams, have provided insights in recent years. In addition, computational methods that deduce unknown structures by learning from known ones have proven remarkably successful — in fact, Google’s artificial-intelligence-based calculation of protein structures was named the Breakthrough of the Year for 2021 by the journal Science.
What are these shapes that proteins adopt? Here are all the atoms and bonds between them in “Caspase 9,”, a protein that helps orchestrate cell death. (Source: Protein data bank structure 1NW9; visualized with UCSF Chimera). It’s not obvious that there’s any pattern or regularity.
If we zoom into the piece at the right edge, it’s still dizzying…
… but if we show only the atoms along the spine of the protein molecule — the chain that makes it a chain-like molecule — and strip off the atoms that branch off to the sides, we see a simple spiral:
This “alpha helix” is so common among the shapes nature’s proteins adopt that it’s part of a standard, stylized pictorial library for depicting proteins:
Sheets are another common motif, and both helices and sheets are evident in the overall Caspase-9 structure, which I’ve painted here.
In addition to often being elegant, protein structures are important — they influence how proteins bind to one another, conduct chemical reactions and perform the tasks they’re called on to do. How do these shapes arise? That question will have to wait…
All this is elaborated in Chapter 2 of So Simple a Beginning— “Proteins: Molecular Origami” . There I also describe the forces that sculpt proteins, how the combination of cannibalism and proteins with the wrong shape led to devastating disease outbreaks, and more.
— Raghuveer Parthasarathy; December 24, 2021
The Eighteenth Elephant 