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Accommodation of a highly symmetric core within a symmetric protein superfold
Author(s) -
Brych Stephen R.,
Kim Jaewon,
Logan Timothy M.,
Blaber Michael
Publication year - 2003
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.03374903
Subject(s) - trefoil , complementarity (molecular biology) , asymmetry , core (optical fiber) , protein structure , protein tertiary structure , physics , mathematics , combinatorics , crystallography , chemistry , biology , genetics , optics , nuclear magnetic resonance , quantum mechanics , agronomy
Abstract An alternative core packing group, involving a set of five positions, has been introduced into human acidic FGF‐1. This alternative group was designed so as to constrain the primary structure within the core region to the same threefold symmetry present in the tertiary structure of the protein fold (the β‐trefoil superfold). The alternative core is essentially indistinguishable from the WT core with regard to structure, stability, and folding kinetics. The results show that the β‐trefoil superfold is compatible with a threefold symmetric constraint on the core region, as might be the case if the superfold arose as a result of gene duplication/fusion events. Furthermore, this new core arrangement can form the basis of a structural “building block” that can greatly simplify the de novo design of β‐trefoil proteins by using symmetric structural complementarity. Remaining asymmetry within the core appears to be related to asymmetry in the tertiary structure associated with receptor and heparin binding functionality of the growth factor.