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Mutation in a flexible linker modulates binding affinity for modular complexes
Author(s) -
Stokes Philippa H.,
Robertson Neil O.,
Silva Ana P. G.,
Estephan Tanya,
Trewhella Jill,
Guss J. Mitchell,
Matthews Jacqueline M.
Publication year - 2019
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.25675
Subject(s) - linker , tandem , side chain , chemistry , stereochemistry , modular design , biophysics , modularity (biology) , binding site , crystallography , genetics , biochemistry , biology , materials science , computer science , composite material , operating system , organic chemistry , polymer
Tandem beta zippers are modular complexes formed between repeated linear motifs and tandemly arrayed domains of partner proteins in which β‐strands form upon binding. Studies of such complexes, formed by LIM domain proteins and linear motifs in their intrinsically disordered partners, revealed spacer regions between the linear motifs that are relatively flexible but may affect the overall orientation of the binding modules. We demonstrate that mutation of a solvent exposed side chain in the spacer region of an LHX4–ISL2 complex has no significant effect on the structure of the complex, but decreases binding affinity, apparently by increasing flexibility of the linker.