Three-dimensional structures of membrane proteins from genomic sequencing.

Cell
Thomas A HopfDebora S Marks

Abstract

We show that amino acid covariation in proteins, extracted from the evolutionary sequence record, can be used to fold transmembrane proteins. We use this technique to predict previously unknown 3D structures for 11 transmembrane proteins (with up to 14 helices) from their sequences alone. The prediction method (EVfold_membrane) applies a maximum entropy approach to infer evolutionary covariation in pairs of sequence positions within a protein family and then generates all-atom models with the derived pairwise distance constraints. We benchmark the approach with blinded de novo computation of known transmembrane protein structures from 23 families, demonstrating unprecedented accuracy of the method for large transmembrane proteins. We show how the method can predict oligomerization, functional sites, and conformational changes in transmembrane proteins. With the rapid rise in large-scale sequencing, more accurate and more comprehensive information on evolutionary constraints can be decoded from genetic variation, greatly expanding the repertoire of transmembrane proteins amenable to modeling by this method.

References

Sep 30, 1992·Biochemical and Biophysical Research Communications·D R JohnsR D Park
Feb 14, 1971·Journal of Molecular Biology·B Lee, F M Richards
Mar 1, 1995·Protein Science : a Publication of the Protein Society·B RostC Sander
Apr 1, 1994·Proteins·U GöbelA Valencia
Jul 20, 1993·Journal of Molecular Biology·B Rost, C Sander
Sep 5, 1993·Journal of Molecular Biology·L Holm, C Sander
Jan 1, 1993·Protein Engineering·P CronetG Vriend
Nov 1, 1995·Trends in Biochemical Sciences·L Holm, C Sander
Aug 1, 1996·Protein Science : a Publication of the Protein Society·B RostR Casadio
Oct 3, 1998·Acta Crystallographica. Section D, Biological Crystallography·A T BrüngerG L Warren
Dec 23, 1998·Proceedings of the National Academy of Sciences of the United States of America·L A DoyleD D Ross
Dec 10, 1999·Proceedings of the National Academy of Sciences of the United States of America·R Srinivasan, G D Rose
Dec 11, 1999·Nucleic Acids Research·H M BermanP E Bourne
Mar 27, 2001·Protein Science : a Publication of the Protein Society·S JayasingheS H White
Apr 24, 2002·Physical Review. E, Statistical Physics, Plasmas, Fluids, and Related Interdisciplinary Topics·B G GiraudA S Lapedes
Jun 13, 2003·Nature·Toshimasa YamauchiTakashi Kadowaki
Jun 26, 2003·Nucleic Acids Research·Adam Zemla
Apr 27, 2004·Nature Genetics·Vanya D PeltekovaKatherine A Siminovitch
Jun 25, 2004·Nucleic Acids Research·Yuzhen Ye, Adam Godzik
Dec 21, 2004·Nucleic Acids Research·Gábor E TusnádyIstván Simon
Apr 26, 2005·Nucleic Acids Research·Yang Zhang, Jeffrey Skolnick
Sep 15, 2005·Journal of Electron Microscopy·M Joanne LemieuxDa Neng Wang
Sep 24, 2005·Nature·William P RussRama Ranganathan
Dec 24, 2005·Proteins·Vladimir Yarov-YarovoyDavid Baker
Dec 2, 2006·Proceedings of the National Academy of Sciences of the United States of America·Timothy R LezonNina V Fedoroff
Dec 2, 2006·Nature Reviews. Drug Discovery·John P OveringtonAndrew L Hopkins
Oct 24, 2007·Nature·Søren G F RasmussenBrian K Kobilka
Nov 17, 2007·Nature Protocols·Axel T Brunger
Nov 21, 2007·Proceedings of the National Academy of Sciences of the United States of America·Andrew WardGeoffrey Chang
Dec 11, 2007·Bioinformatics·Angelika FuchsDmitrij Frishman
Apr 9, 2008·Journal of Molecular Biology·Christopher J LawDa-Neng Wang

❮ Previous
Next ❯

Citations

Sep 26, 2012·Journal of Biomolecular NMR·Ye TianFrancesca M Marassi
Nov 10, 2012·Nature Biotechnology·Debora S MarksChris Sander
Jul 16, 2013·Nature Biotechnology·Soheil FeiziManolis Kellis
Jan 8, 2013·Nature Methods·Henry LinBrian K Shoichet
Mar 6, 2013·Nature Reviews. Genetics·David de JuanAlfonso Valencia
Feb 6, 2013·Nature Structural & Molecular Biology·Ursula PieperAndrej Sali
Sep 7, 2013·Proceedings of the National Academy of Sciences of the United States of America·Hetunandan KamisettyDavid Baker
Mar 21, 2013·Genome Biology and Evolution·Eric A FranzosaYu Xia
Oct 19, 2012·Protein Engineering, Design & Selection : PEDS·Chan-Seok Jeong, Dongsup Kim
Nov 6, 2013·Acta Crystallographica. Section D, Biological Crystallography·Chantal Abergel
Sep 21, 2013·BMC Bioinformatics·Timothy Nugent, David T Jones
May 24, 2014·PLoS Computational Biology·Kuang-Yui M ChenPatrick Barth
Mar 29, 2014·BMC Bioinformatics·László KajánBurkhard Rost
Sep 3, 2013·Cellular and Molecular Life Sciences : CMLS·Inga SandlerAmir Aharoni
Jan 29, 2014·The Journal of General Physiology·Eugene PalovcakVincenzo Carnevale
Dec 20, 2013·Algorithms for Molecular Biology : AMB·Witold DyrkaMalgorzata Kotulska
Dec 4, 2013·Proceedings of the National Academy of Sciences of the United States of America·Faruck MorcosJosé N Onuchic
Nov 19, 2013·Acta Pharmacologica Sinica·Joseph J Babcock, Min Li
May 24, 2014·Archives of Biochemistry and Biophysics·Jessica Andreani, Raphael Guerois
Sep 1, 2014·Nature Methods·Lauren C ChongPaul C Boutros
Aug 28, 2014·Bioinformatics·Mirco MichelArne Elofsson
Jul 27, 2014·Nucleic Acids Research·Songling LiDaron M Standley
Jan 1, 2013·Computational and Structural Biotechnology Journal·Amanda M Duran, Jens Meiler
Jan 19, 2016·Nature Chemical Biology·Xiang Feng, Patrick Barth
Dec 22, 2015·Protein Engineering, Design & Selection : PEDS·Guillaume PosticJean-Christophe Gelly
Dec 19, 2015·Journal of the American Chemical Society·Steven S KlaraMeagan S Mauter
Apr 11, 2015·Proceedings of the National Academy of Sciences of the United States of America·Sikander HayatArne Elofsson
Feb 9, 2016·Nature Structural & Molecular Biology·Matthew A B BakerLawrence K Lee
May 18, 2013·Current Opinion in Structural Biology·William R TaylorMichael I Sadowski
Oct 9, 2015·Molecular Biology and Evolution·Matteo FigliuzziMartin Weigt

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cajal Bodies & Gems

Cajal bodies or coiled bodies are dense foci of coilin protein. Gemini of Cajal bodies, or gems, are microscopically similar to Cajal bodies. It is believed that Cajal bodies play important roles in RNA processing while gems assist the Cajal bodies. Find the latest research on Cajal bodies and gems here.

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Cell eTOC

Cell is a scientific journal publishing research across a broad range of disciplines within the life sciences field. Discover the latest research from Cell here.