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Steric restrictions in protein folding: An α‐helix cannot be followed by a contiguous β‐strand
Author(s) -
Fitzkee Nicholas C.,
Rose George D.
Publication year - 2004
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.03503304
Subject(s) - steric effects , dihedral angle , protein folding , linker , folding (dsp implementation) , chemistry , crystallography , protein structure , limiting , dipeptide , biophysics , stereochemistry , peptide , biology , biochemistry , computer science , molecule , mechanical engineering , hydrogen bond , organic chemistry , electrical engineering , engineering , operating system
Using only hard‐sphere repulsion, we investigated short polyalanyl chains for the presence of sterically imposed conformational constraints beyond the dipeptide level. We found that a central residue in a helical peptide cannot adopt dihedral angles from strand regions without encountering a steric collision. Consequently, an α‐helical segment followed by a β‐strand segment must be connected by an intervening linker. This restriction was validated both by simulations and by seeking violations within proteins of known structure. In fact, no violations were found within an extensive database of high‐resolution X‐ray structures. Nature's exclusion of α‐β hybrid segments, fashioned from an α‐helix adjoined to a β‐strand, is built into proteins at the covalent level. This straightforward conformational constraint has far‐reaching consequences in organizing unfolded proteins and limiting the number of possible protein domains.