Analyses of displacements resulting from a point mutation in proteins.

Journal of Structural Biology
Mathilde Carpentier, Jacques Chomilier

Abstract

The effects of a single residue substitution on the protein backbone are frequently quite small and there are many other potential sources of structural variation for protein. We present here a methodology considering different sources of distortions in order to isolate the very effect of the mutation. To validate our methodology, we consider a well-studied family with many single mutants: the human lysozyme. Most of the perturbations are expected to be at the very localisation of the mutation, but in many cases the effects are propagated at long range. We show that the distances between the mutated residue and the 5% most disturbed residues exponentially decreases. One third of the affected residues are in direct contact with the mutated position; the remaining two thirds are potential allosteric effects. We confirm the reliability of the residues identified as significantly perturbed by comparing our results to experimental studies. We confirm with the present method all the previously identified perturbations. This study shows that mutations have long-range impact on protein backbone that can be detected, although the displacement of the affected atoms is small.

References

Apr 21, 1991·Journal of Theoretical Biology·E I Shakhnovich, A M Gutin
Dec 1, 1995·Proteins·D Frishman, P Argos
Feb 27, 1999·Journal of Molecular Biology·B L de GrootH J Berendsen
Dec 11, 1999·Nucleic Acids Research·H M BermanP E Bourne
Apr 3, 2002·The Journal of Biological Chemistry·Jun FunahashiKatsuhide Yutani
Jul 12, 2002·American Journal of Human Genetics·B V NorthP C Sham
Mar 4, 2003·Journal of Molecular Evolution·Ugo BastollaMichele H Vendruscolo
Aug 12, 2003·Journal of Molecular Biology·Gail J BartlettJanet M Thornton
Jun 28, 2005·Nucleic Acids Research·C AllandP Tufféry
Mar 29, 2007·Proceedings of the National Academy of Sciences of the United States of America·Ruhong ZhouBruce J Berne
Oct 5, 2007·Journal of Biosciences·Richard Lavery, Sophie Sacquin-Mora
Nov 16, 2007·Proteins·Mickey Kosloff, Rachel Kolodny
Jul 21, 2009·Biochemical Society Transactions·Sungsam GongTom L Blundell
Oct 20, 2009·Structure·Donald S BerkholzP Andrew Karplus
Apr 1, 2010·Nature Methods·Ivan A AdzhubeiShamil R Sunyaev
Mar 19, 2011·BMC Bioinformatics·Xavier RobinMarkus Müller
May 3, 2011·Journal of the American Chemical Society·Alexander K BuellChristopher M Dobson
Oct 1, 2011·Nature Methods·Thomas Nordahl PetersenHenrik Nielsen
Jan 19, 2013·Molecular Biology and Evolution·Kazutaka Katoh, Daron M Standley
Dec 14, 2016·Biochemistry·Nandakumar RajasekaranAthi N Naganathan
Dec 15, 2016·Journal of Molecular Biology·Harry C JubbTom L Blundell
Sep 7, 2017·Protein Science : a Publication of the Protein Society·Roman A LaskowskiJanet M Thornton
Mar 24, 2018·Proteins·Suvethigaa ShanthirabalanMathilde Carpentier

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Citations

Sep 14, 2021·ACS Omega·Fatemeh SahebazzamaniHoward O Fearnhead

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