A topological and conformational stability alphabet for multipass membrane proteins

Nature Chemical Biology
Xiang Feng, Patrick Barth

Abstract

Multipass membrane proteins perform critical signal transduction and transport across membranes. How transmembrane helix (TMH) sequences encode the topology and conformational flexibility regulating these functions remains poorly understood. Here we describe a comprehensive analysis of the sequence-structure relationships at multiple interacting TMHs from all membrane proteins with structures in the Protein Data Bank (PDB). We found that membrane proteins can be deconstructed in interacting TMH trimer units, which mostly fold into six distinct structural classes of topologies and conformations. Each class is enriched in recurrent sequence motifs from functionally unrelated proteins, revealing unforeseen consensus and evolutionary conserved networks of stabilizing interhelical contacts. Interacting TMHs' topology and local protein conformational flexibility were remarkably well predicted in a blinded fashion from the identified binding-hotspot motifs. Our results reveal universal sequence-structure principles governing the complex anatomy and plasticity of multipass membrane proteins that may guide de novo structure prediction, design, and studies of folding and dynamics.

References

Jun 1, 1997·Protein Science : a Publication of the Protein Society·E WolfB Berger
Nov 22, 1997·Journal of Molecular Biology·J U Bowie
May 26, 1998·Journal of Molecular Biology·M PetukhovL Serrano
Aug 12, 1998·Journal of Molecular Biology·C Bystroff, D Baker
Mar 27, 2001·Protein Science : a Publication of the Protein Society·S JayasingheS H White
Oct 5, 2001·The Journal of Biological Chemistry·R Gurezka, D Langosch
Sep 7, 2006·Proceedings of the National Academy of Sciences of the United States of America·R F S Walters, W F DeGrado
Nov 4, 2006·Cell·Erin E MatthewsDonald M Engelman
Dec 2, 2006·Nature Reviews. Molecular Cell Biology·Gunnar von Heijne
Oct 2, 2007·Proceedings of the National Academy of Sciences of the United States of America·P BarthD Baker
Apr 3, 2008·PloS One·Hongbo ZhuFrancisco S Domingues
Sep 25, 2008·Proceedings of the National Academy of Sciences of the United States of America·Casim A SarkarAndreas Plückthun
Feb 5, 2009·Proceedings of the National Academy of Sciences of the United States of America·P BarthD Baker
May 22, 2009·Nature·Harini KrishnamurthyEric Gouaux
Jun 17, 2009·Protein Science : a Publication of the Protein Society·Dieter Langosch, Isaiah T Arkin
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Vincent B ChenDavid C Richardson
Feb 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Tobin J CammettDaniel Dimaio
Nov 26, 2010·Journal of Molecular Biology·Elizabeth P RakoczyLuis Serrano
Apr 12, 2011·Nature Biotechnology·Roslyn M BillHorst Vogel
Oct 28, 2011·Proceedings of the National Academy of Sciences of the United States of America·Ron O DrorDavid E Shaw
May 31, 2012·Proceedings of the National Academy of Sciences of the United States of America·Timothy Nugent, David T Jones
Aug 1, 2012·Proceedings of the National Academy of Sciences of the United States of America·Kuang-Yui Michael ChenPatrick Barth
Sep 7, 2012·PLoS Computational Biology·Jessica AndreaniRaphaël Guerois
Nov 9, 2012·Nature·Nobuyasu KogaDavid Baker
Nov 10, 2012·Nature Biotechnology·Debora S MarksChris Sander
Dec 4, 2012·Nucleic Acids Research·Dániel KozmaGábor E Tusnády
Feb 27, 2014·Proceedings of the National Academy of Sciences of the United States of America·Benjamin K MuellerAlessandro Senes
Oct 4, 2014·Journal of Molecular Biology·Florian CymerStephen H White
Dec 20, 2014·Science·Nathan H JohWilliam F DeGrado

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Citations

Nov 5, 2016·Proceedings of the National Academy of Sciences of the United States of America·Craig O MackenzieGevorg Grigoryan
Jun 8, 2017·Biophysical Journal·Omar B Sanchez-ReyesSteven O Smith
Jun 9, 2016·Nature Structural & Molecular Biology·Patrick Barth, Alessandro Senes
Jun 21, 2017·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Nathan H JohWilliam F DeGrado
Jun 21, 2017·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Ai NiitsuDerek N Woolfson
Nov 2, 2019·Biochemical Society Transactions·Paul Curnow
May 30, 2017·PloS One·Fan Zheng, Gevorg Grigoryan
May 2, 2017·Current Opinion in Structural Biology·Craig O Mackenzie, Gevorg Grigoryan
Jul 17, 2021·Journal of Molecular Biology·Anastassia Andreevna Vorobieva

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