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Understanding a protein fold: The physics, chemistry, and biology of a-helical coiled coils.
- Source :
-
Journal of Biological Chemistry . Apr2023, Vol. 299 Issue 4, p1-25. 25p. - Publication Year :
- 2023
-
Abstract
- Protein science is being transformed by powerful computational methods for structure prediction and design: AlphaFold2 can predict many natural protein structures from sequence, and other AI methods are enabling the de novo design of new structures. This raises a question: how much do we understand the underlying sequence-to-structure/function relationships being captured by these methods? This perspective presents our current understanding of one class of protein assembly, the a-helical coiled coils. At first sight, these are straightforward: sequence repeats of hydrophobic (h) and polar (p) residues, (hpphppp)n, direct the folding and assembly of amphipathic a helices into bundles. However, many different bundles are possible: they can have two or more helices (different oligomers); the helices can have parallel, antiparallel, or mixed arrangements (different topologies); and the helical sequences can be the same (homomers) or different (heteromers). Thus, sequence-to-structure relationships must be present within the hpphppp repeats to distinguish these states. I discuss the current understanding of this problem at three levels: first, physics gives a parametric framework to generate the many possible coiled-coil backbone structures. Second, chemistry provides a means to explore and deliver sequence-to-structure relationships. Third, biology shows how coiled coils are adapted and functionalized in nature, inspiring applications of coiled coils in synthetic biology. I argue that the chemistry is largely understood; the physics is partly solved, though the considerable challenge of predicting even relative stabilities of different coiled-coil states remains; but there is much more to explore in the biology and synthetic biology of coiled coils. [ABSTRACT FROM AUTHOR]
- Subjects :
- *PROTEIN folding
*SYNTHETIC biology
*PROTEIN structure
*PHYSICS
*BIOLOGY
*OLIGOMERS
Subjects
Details
- Language :
- English
- ISSN :
- 00219258
- Volume :
- 299
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Journal of Biological Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 164000651
- Full Text :
- https://doi.org/10.1016/j.jbc.2023.104579