Journal article

Mutations at protein-protein interfaces: Small changes over big surfaces have large impacts on human health

Harry C Jubb, Arun P Pandurangan, Meghan A Turner, Bernardo Ochoa-Montano, Tom L Blundell, David B Ascher

PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY | PERGAMON-ELSEVIER SCIENCE LTD | Published : 2017

Abstract

Many essential biological processes including cell regulation and signalling are mediated through the assembly of protein complexes. Changes to protein-protein interaction (PPI) interfaces can affect the formation of multiprotein complexes, and consequently lead to disruptions in interconnected networks of PPIs within and between cells, further leading to phenotypic changes as functional interactions are created or disrupted. Mutations altering PPIs have been linked to the development of genetic diseases including cancer and rare Mendelian diseases, and to the development of drug resistance. The importance of these protein mutations has led to the development of many resources for understand..

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Grants

Awarded by Biotechnology and Biological Sciences Research Council and UCB


Awarded by C. J. Martin Research Fellowship from the National Health and Medical Research Council of Australia


Awarded by Jack Brockhoff Foundation


Awarded by Fundacao de Amparo a Pesquisa do Estado de Minas Gerais


Awarded by MRC


Awarded by Biotechnology and Biological Sciences Research Council


Awarded by Medical Research Council


Funding Acknowledgements

H.J. was supported by the Biotechnology and Biological Sciences Research Council and UCB [BB/J500574/1] and is currently funded by an Astex Pharmaceuticals Sustaining Innovation Postdoctoral Fellowship hosted at the Wellcome Trust Sanger Institute. M.A.T was supported by scholarships from Promega Corporation, as well as the College of Agricultural and Life Sciences and the Department of Biochemistry at the University of Wisconsin-Madison, USA. B.O.M was supported by the Bill and Melinda Gates Foundation. D.B.A is the recipient of a C. J. Martin Research Fellowship from the National Health and Medical Research Council of Australia (APP1072476) and is funded by the Wellcome Trust and Jack Brockhoff Foundation (JBF 4186, 2016). D.B.A. and T.L.B. are funded by a Newton Fund RCUK-CONFAP Grant awarded by The Medical Research Council and Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (MR/M026302/1). T.L.B. receives funding from the University of Cambridge and The Wellcome Trust for facilities and support.