Mutation in a flexible linker modulates binding affinity for modular complexes

Proteins
Philippa H StokesJacqueline M Matthews

Abstract

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.

References

May 1, 1997·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson
Sep 3, 2004·The EMBO Journal·Janet E DeaneJacqueline M Matthews
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Feb 1, 2011·The Journal of Biological Chemistry·Batiste BoëdaMichael Way
Jan 22, 2013·FEBS Letters·Jacqueline M Matthews, Jennifer R Potts
Jun 12, 2013·The Journal of Biological Chemistry·Morgan S GaddJacqueline M Matthews
Jun 26, 2013·Acta Crystallographica. Section D, Biological Crystallography·Philip R Evans, Garib N Murshudov
Sep 21, 2016·Angewandte Chemie·Neil O RobertsonJacqueline M Matthews
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor
Sep 7, 2017·Acta Crystallographica. Section D, Structural Biology·Jill TrewhellaAndrew E Whitten
Apr 19, 2018·Proceedings of the National Academy of Sciences of the United States of America·Neil O RobertsonJacqueline M Matthews

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Citations

Apr 4, 2021·International Journal of Molecular Sciences·M Quadir SiddiquiTrushar R Patel

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