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Publication Abstract from PubMed

Although folded proteins are commonly depicted as simplistic combinations of beta-strands and alpha-helices, the actual properties and functions of these secondary-structure elements in their native contexts are just partly understood. The principal reason is that the behavior of individual beta- and alpha-elements is obscured by the global folding cooperativity. In this study, we have circumvented this problem by designing frustrated variants of the mixed alpha/beta-protein S6, which allow the structural behavior of individual beta-strands and alpha-helices to be targeted selectively by stopped-flow kinetics, X-ray crystallography, and solution-state NMR. Essentially, our approach is based on provoking intramolecular "domain swap." The results show that the alpha- and beta-elements have quite different characteristics: The swaps of beta-strands proceed via global unfolding, whereas the alpha-helices are free to swap locally in the native basin. Moreover, the alpha-helices tend to hybridize and to promote protein association by gliding over to neighboring molecules. This difference in structural behavior follows directly from hydrogen-bonding restrictions and suggests that the protein secondary structure defines not only tertiary geometry, but also maintains control in function and structural evolution. Finally, our alternative approach to protein folding and native-state dynamics presents a generally applicable strategy for in silico design of protein models that are computationally testable in the microsecond-millisecond regime.

Exposing the distinctive modular behavior of beta-strands and alpha-helices in folded proteins.,Wang H, Logan DT, Danielsson J, Oliveberg M Proc Natl Acad Sci U S A. 2020 Nov 17;117(46):28775-28783. doi:, 10.1073/pnas.1920455117. Epub 2020 Nov 4. PMID:33148805^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.