Anatomy of protein disorder, flexibility and disease-related mutations

Frontiers in Molecular Biosciences
Hui-Chun LuFranca Fraternali

Abstract

Integration of protein structural information with human genetic variation and pathogenic mutations is essential to understand molecular mechanisms associated with the effects of polymorphisms on protein interactions and cellular processes. We investigate occurrences of non-synonymous SNPs in ordered and disordered protein regions by systematic mapping of common variants and disease-related SNPs onto these regions. We show that common variants accumulate in disordered regions; conversely pathogenic variants are significantly depleted in disordered regions. These different occurrences of pathogenic and common SNPs can be attributed to a negative selection on random mutations in structurally highly constrained regions. New approaches in the study of quantitative effects of pathogenic-related mutations should effectively account for all the possible contexts and relative functional constraints in which the sequence variation occurs.

References

Jan 11, 2000·Nucleic Acids Research·S T SherryK Sirotkin
Oct 17, 2002·Journal of Molecular Biology·Lilia M IakouchevaA Keith Dunker
Mar 27, 2004·Bioinformatics·Jonathan J WardDavid T Jones
Aug 3, 2004·Nature Medicine·Bert Vogelstein, Kenneth W Kinzler
Oct 20, 2004·Proceedings of the National Academy of Sciences of the United States of America·Paul D Thomas, Anish Kejariwal
Dec 21, 2004·Nucleic Acids Research·Ada HamoshVictor A McKusick
Jun 28, 2005·Nucleic Acids Research·Emidio CapriottiRita Casadio
Sep 20, 2005·Journal of Molecular Biology·Peng YueJohn Moult
May 29, 2007·Nucleic Acids Research·Yana Bromberg, Burkhard Rost
Jan 18, 2008·Genome Biology·Benjamin Schuster-Böckler, Alex Bateman
Jun 25, 2008·Annual Review of Biophysics·Vladimir N UverskyA Keith Dunker
Jul 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·Sara E DobbinsMichael J E Sternberg
Dec 17, 2009·BMC Bioinformatics·Christiam CamachoThomas L Madden
Apr 1, 2010·Nature Methods·Ivan A AdzhubeiShamil R Sunyaev
Jun 15, 2010·Molecular BioSystems·Jessica H Fong, Anna R Panchenko
Oct 19, 2010·Nucleic Acids Research·Simon A ForbesP Andrew Futreal
Apr 26, 2011·Current Opinion in Structural Biology·M Madan BabuJörg Gsponer
May 20, 2011·Nucleic Acids Research·Robert D FinnSean R Eddy
Jul 6, 2011·Nucleic Acids Research·Boris RevaChris Sander
Sep 16, 2011·Molecular BioSystems·Mátyás PajkosZsuzsanna Dosztányi
Nov 11, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Alessandro PandiniJens Kleinjung
Nov 15, 2011·Molecular BioSystems·Vladimir Vacic, Lilia M Iakoucheva
Dec 1, 2011·Nucleic Acids Research·Marco PuntaRobert D Finn
Jul 24, 2012·Nature Structural & Molecular Biology·Rajintha M BandaranayakeStevan R Hubbard
Sep 8, 2012·Nature·UNKNOWN ENCODE Project Consortium
Oct 12, 2012·PLoS Computational Biology·Vladimir VacicLilia M Iakoucheva
Jul 23, 2013·Journal of Molecular Biology·Christopher M Yates, Michael J E Sternberg
Jul 23, 2013·Journal of Molecular Biology·Shannon SteflEmil Alexov
Aug 16, 2013·Proteins·Bohdan MonastyrskyyKrzysztof Fidelis
Nov 12, 2013·Expert Review of Proteomics·Hui-Chun LuFranca Fraternali
Nov 20, 2013·Journal of Chemical Theory and Computation·Arianna ForniliFranca Fraternali
Nov 28, 2013·Bioinformatics·Douglas E V PiresTom L Blundell
Apr 15, 2014·Nucleic Acids Research·Elisa CiliaWim F Vranken
May 9, 2014·Journal of Molecular Biology·Christopher M YatesMichael J E Sternberg
May 17, 2014·Chemical Reviews·Vladimir N UverskyAndreas C Joerger
Jun 25, 2014·Nature Reviews. Cancer·Matthew HolderfieldMartin McMahon
Oct 10, 2014·Nature Reviews. Genetics·Anamaria Necsulea, Henrik Kaessmann
Oct 14, 2014·Seminars in Cell & Developmental Biology·A Keith DunkerChristopher J Oldfield

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Citations

Nov 19, 2015·Protein Science : a Publication of the Protein Society·Hafumi NishiKengo Kinoshita
Sep 30, 2017·Bioinformatics·Matteo TibertiArianna Fornili
Dec 1, 2017·Physical Chemistry Chemical Physics : PCCP·Xiaorong Liu, Jianhan Chen
Jul 24, 2020·Pharmacogenomics·Yoomi ParkJu Han Kim
Jul 27, 2017·The Journal of Physical Chemistry. B·Ryan L MelvinFreddie R Salsbury
Sep 15, 2017·The Journal of Physical Chemistry. B·Xiaorong LiuJianhan Chen

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Software Mentioned

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