BCL::MP-fold: Membrane protein structure prediction guided by EPR restraints

Fischer, Axel W.; Alexander, Nathan S.; Woetzel, Nils; Karakas, Mert; Weiner, Brian E.; Meiler, Jens

doi:10.1002/prot.24801

Title: BCL::MP-fold: Membrane protein structure prediction guided by EPR restraints

Journal Article · Mon Sep 28 00:00:00 EDT 2015 · Proteins

DOI:https://doi.org/10.1002/prot.24801· OSTI ID:1565412

Fischer, Axel W. ^[1]; Alexander, Nathan S. ^[1]; Woetzel, Nils ^[1]; Karakas, Mert ^[2]; Weiner, Brian E. ^[1]; Meiler, Jens ^[1]

Department of Chemistry, Vanderbilt University, Nashville Tennessee 37232; Center for Structural Biology, Vanderbilt University, Nashville Tennessee 37232
Center for Structural Biology, Vanderbilt University, Nashville Tennessee 37232

For many membrane proteins, the determination of their topology remains a challenge for methods like X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy. Electron paramagnetic resonance (EPR) spectroscopy has evolved as an alternative technique to study structure and dynamics of membrane proteins. The present study demonstrates the feasibility of membrane protein topology determination using limited EPR distance and accessibility measurements. The BCL::MP-Fold (BioChemical Library membrane protein fold) algorithm assembles secondary structure elements (SSEs) in the membrane using a Monte Carlo Metropolis (MCM) approach. Sampled models are evaluated using knowledge-based potential functions and agreement with the EPR data and a knowledge-based energy function. Twenty-nine membrane proteins of up to 696 residues are used to test the algorithm. The RMSD100 value of the most accurate model is better than 8 Å for 27, better than 6 Å for 22, and better than 4 Å for 15 of the 29 proteins, demonstrating the algorithms' ability to sample the native topology. The average enrichment could be improved from 1.3 to 2.5, showing the improved discrimination power by using EPR data. Proteins 2015; 83:1947–1962. © 2015 Wiley Periodicals, Inc

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Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States). Oak Ridge Leadership Computing Facility (OLCF); UT-Battelle LLC/ORNL, Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

DOE Contract Number:: AC05-00OR22725

OSTI ID:: 1565412

Journal Information:: Proteins, Vol. 83, Issue 11; ISSN 0887-3585

Publisher:: Wiley

Country of Publication:: United States

Language:: English

References (45)

Transmembrane protein structure: spin labeling of bacteriorhodopsin mutants Altenbach, C.; Marti, T.; Khorana, H. Science, Vol. 248, Issue 4959 https://doi.org/10.1126/science.2160734	journal	June 1990
BCL::MP-Fold: Folding Membrane Proteins through Assembly of Transmembrane Helices Weiner, Brian E.; Woetzel, Nils; Karakaş, Mert Structure, Vol. 21, Issue 7 https://doi.org/10.1016/j.str.2013.04.022	journal	July 2013
Solvent accessible surface area approximations for rapid and accurate protein structure prediction Durham, Elizabeth; Dorr, Brent; Woetzel, Nils Journal of Molecular Modeling, Vol. 15, Issue 9 https://doi.org/10.1007/s00894-009-0454-9	journal	February 2009
Solution NMR study of integral membrane proteins Kang, CongBao; Li, Qingxin Current Opinion in Chemical Biology, Vol. 15, Issue 4 https://doi.org/10.1016/j.cbpa.2011.05.025	journal	August 2011
Recent advances in the application of solution NMR spectroscopy to multi-span integral membrane proteins Kim, Hak Jun; Howell, Stanley C.; Van Horn, Wade D. Progress in Nuclear Magnetic Resonance Spectroscopy, Vol. 55, Issue 4 https://doi.org/10.1016/j.pnmrs.2009.07.002	journal	November 2009
BCL::Fold - De Novo Prediction of Complex and Large Protein Topologies by Assembly of Secondary Structure Elements Karakaş, Mert; Woetzel, Nils; Staritzbichler, Rene PLoS ONE, Vol. 7, Issue 11 https://doi.org/10.1371/journal.pone.0049240	journal	November 2012
Engineering G protein-coupled receptors to facilitate their structure determination Tate, Christopher G.; Schertler, Gebhard FX Current Opinion in Structural Biology, Vol. 19, Issue 4 https://doi.org/10.1016/j.sbi.2009.07.004	journal	August 2009
Structural Dynamics of the Magnesium-Bound Conformation of CorA in a Lipid Bilayer Dalmas, Olivier; Cuello, Luis G.; Jogini, Vishwanath Structure, Vol. 18, Issue 7 https://doi.org/10.1016/j.str.2010.04.009	journal	July 2010
Energetic analysis of the rhodopsin–G-protein complex links the α5 helix to GDP release Alexander, Nathan S.; Preininger, Anita M.; Kaya, Ali I. Nature Structural & Molecular Biology, Vol. 21, Issue 1 https://doi.org/10.1038/nsmb.2705	journal	December 2013
De Novo High-Resolution Protein Structure Determination from Sparse Spin-Labeling EPR Data Alexander, Nathan; Al-Mestarihi, Ahmad; Bortolus, Marco Structure, Vol. 16, Issue 2 https://doi.org/10.1016/j.str.2007.11.015	journal	February 2008
Ion/substrate-dependent conformational dynamics of a bacterial homolog of neurotransmitter:sodium symporters Claxton, Derek P.; Quick, Matthias; Shi, Lei Nature Structural & Molecular Biology, Vol. 17, Issue 7 https://doi.org/10.1038/nsmb.1854	journal	June 2010
Transmembrane proteins in the Protein Data Bank: identification and classification Tusnady, G. E.; Dosztanyi, Z.; Simon, I. Bioinformatics, Vol. 20, Issue 17 https://doi.org/10.1093/bioinformatics/bth340	journal	June 2004
OCTOPUS: improving topology prediction by two-track ANN-based preference scores and an extended topological grammar Viklund, Håkan; Elofsson, Arne Bioinformatics, Vol. 24, Issue 15 https://doi.org/10.1093/bioinformatics/btn221	journal	May 2008
Folding pattern of the α-crystallin domain in αA-crystallin determined by site-directed spin labeling Koteiche, Hanane A.; Mchaourab, Hassane S. Journal of Molecular Biology, Vol. 294, Issue 2 https://doi.org/10.1006/jmbi.1999.3242	journal	November 1999
EM-Fold: De Novo Atomic-Detail Protein Structure Determination from Medium-Resolution Density Maps Lindert, Steffen; Alexander, Nathan; Wötzel, Nils Structure, Vol. 20, Issue 3 https://doi.org/10.1016/j.str.2012.01.023	journal	March 2012
Multipass membrane protein structure prediction using Rosetta Yarov-Yarovoy, Vladimir; Schonbrun, Jack; Baker, David Proteins: Structure, Function, and Bioinformatics, Vol. 62, Issue 4 https://doi.org/10.1002/prot.20817	journal	December 2005
Structural Basis of Energy Transduction in the Transport Cycle of MsbA Dong, J. Science, Vol. 308, Issue 5724 https://doi.org/10.1126/science.1106592	journal	May 2005
Three-Dimensional Architecture of Membrane-Embedded MscS in the Closed Conformation Vásquez, Valeria; Sotomayor, Marcos; Marien Cortes, D. Journal of Molecular Biology, Vol. 378, Issue 1 https://doi.org/10.1016/j.jmb.2007.10.086	journal	April 2008
Distance measurements on spin-labelled biomacromolecules by pulsed electron paramagnetic resonance Jeschke, Gunnar; Polyhach, Yevhen Physical Chemistry Chemical Physics, Vol. 9, Issue 16 https://doi.org/10.1039/b614920k	journal	January 2007
Structural Dynamics of an Isolated Voltage-Sensor Domain in a Lipid Bilayer Chakrapani, Sudha; Cuello, Luis G.; Cortes, D. Marien Structure, Vol. 16, Issue 3 https://doi.org/10.1016/j.str.2007.12.015	journal	March 2008
How many drug targets are there? Overington, John P.; Al-Lazikani, Bissan; Hopkins, Andrew L. Nature Reviews Drug Discovery, Vol. 5, Issue 12 https://doi.org/10.1038/nrd2199	journal	December 2006
Prediction of membrane protein structures with complex topologies using limited constraints Barth, P.; Wallner, B.; Baker, D. Proceedings of the National Academy of Sciences, Vol. 106, Issue 5 https://doi.org/10.1073/pnas.0808323106	journal	February 2009
Simultaneous prediction of protein secondary structure and transmembrane spans: Secondary Structure Prediction in Membranes Leman, Julia Koehler; Mueller, Ralf; Karakas, Mert Proteins: Structure, Function, and Bioinformatics, Vol. 81, Issue 7 https://doi.org/10.1002/prot.24258	journal	April 2013
Practical Considerations of Membrane Protein Instability during Purification and Crystallisation Tate, Christopher G. Heterologous Expression of Membrane Proteins. Methods in Molecular Biology https://doi.org/10.1007/978-1-60761-344-2_12	book	October 2009
Structure in the channel forming domain of colicin E1 bound to membranes: The 402-424 sequence SalwiSki, Ukasz; Hubbell, Wayne L. Protein Science, Vol. 8, Issue 3 https://doi.org/10.1110/ps.8.3.562	journal	January 1999
RosettaEPR: An integrated tool for protein structure determination from sparse EPR data Hirst, Stephanie J.; Alexander, Nathan; Mchaourab, Hassane S. Journal of Structural Biology, Vol. 173, Issue 3 https://doi.org/10.1016/j.jsb.2010.10.013	journal	March 2011
EM-Fold: De Novo Folding of α-Helical Proteins Guided by Intermediate-Resolution Electron Microscopy Density Maps Lindert, Steffen; Staritzbichler, René; Wötzel, Nils Structure, Vol. 17, Issue 7 https://doi.org/10.1016/j.str.2009.06.001	journal	July 2009
The Protein Data Bank Berman, H. M. Nucleic Acids Research, Vol. 28, Issue 1 https://doi.org/10.1093/nar/28.1.235	journal	January 2000
Motion of Spin Label Side Chains in Cellular Retinol-Binding Protein: Correlation with Structure and Nearest-Neighbor Interactions in an Antiparallel β-Sheet ^† Lietzow, Michael A.; Hubbell, Wayne L. Biochemistry, Vol. 43, Issue 11 https://doi.org/10.1021/bi0360962	journal	March 2004
Overcoming barriers to membrane protein structure determination Bill, Roslyn M.; Henderson, Peter J. F.; Iwata, So Nature Biotechnology, Vol. 29, Issue 4 https://doi.org/10.1038/nbt.1833	journal	April 2011
Protein Structure Determination Using Long-Distance Constraints from Double-Quantum Coherence ESR: Study of T4 Lysozyme Borbat, Petr P.; Mchaourab, Hassane S.; Freed, Jack H. Journal of the American Chemical Society, Vol. 124, Issue 19 https://doi.org/10.1021/ja020040y	journal	May 2002
Combining NMR and EPR Methods for Homodimer Protein Structure Determination Yang, Yunhuang; Ramelot, Theresa A.; McCarrick, Robert M. Journal of the American Chemical Society, Vol. 132, Issue 34 https://doi.org/10.1021/ja105080h	journal	September 2010
Identification of Protein Folding Patterns Using Site-Directed Spin Labeling. Structural Characterization of a β-Sheet and Putative Substrate Binding Regions in the Conserved Domain of αA-Crystallin ^† Koteiche, Hanane A.; Berengian, Anderee R.; Mchaourab, Hassane S. Biochemistry, Vol. 37, Issue 37 https://doi.org/10.1021/bi9814078	journal	September 1998
BCL::Fold-Protein topology determination from limited NMR restraints: Protein Topology from Limited NMR Restraints Weiner, Brian E.; Alexander, Nathan; Akin, Louesa R. Proteins: Structure, Function, and Bioinformatics, Vol. 82, Issue 4 https://doi.org/10.1002/prot.24427	journal	October 2013
The activated state of a sodium channel voltage sensor in a membrane environment Chakrapani, S.; Sompornpisut, P.; Intharathep, P. Proceedings of the National Academy of Sciences, Vol. 107, Issue 12 https://doi.org/10.1073/pnas.0914109107	journal	March 2010
G protein coupled receptor structure and activation Kobilka, Brian K. Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1768, Issue 4 https://doi.org/10.1016/j.bbamem.2006.10.021	journal	April 2007
BCL::Score—Knowledge Based Energy Potentials for Ranking Protein Models Represented by Idealized Secondary Structure Elements Woetzel, Nils; Karakaş, Mert; Staritzbichler, Rene PLoS ONE, Vol. 7, Issue 11 https://doi.org/10.1371/journal.pone.0049242	journal	November 2012
Algorithm for selection of optimized EPR distance restraints for de novo protein structure determination Kazmier, Kelli; Alexander, Nathan S.; Meiler, Jens Journal of Structural Biology, Vol. 173, Issue 3 https://doi.org/10.1016/j.jsb.2010.11.003	journal	March 2011
Toward high-resolution prediction and design of transmembrane helical protein structures Barth, P.; Schonbrun, J.; Baker, D. Proceedings of the National Academy of Sciences, Vol. 104, Issue 40 https://doi.org/10.1073/pnas.0702515104	journal	September 2007
Investigation of structure and dynamics in membrane proteins using site-directed spin labeling Hubbell, Wayne L.; Altenbach, Christian Current Opinion in Structural Biology, Vol. 4, Issue 4 https://doi.org/10.1016/S0959-440X(94)90219-4	journal	January 1994
Structural Features and Light-Dependent Changes in the Cytoplasmic Interhelical E−F Loop Region of Rhodopsin: A Site-Directed Spin-Labeling Study ^† Altenbach, Christian; Yang, Ke; Farrens, David L. Biochemistry, Vol. 35, Issue 38 https://doi.org/10.1021/bi960849l	journal	January 1996
Alternating Access of the Putative Substrate-Binding Chamber in the ABC Transporter MsbA Zou, Ping; Mchaourab, Hassane S. Journal of Molecular Biology, Vol. 393, Issue 3 https://doi.org/10.1016/j.jmb.2009.08.051	journal	October 2009
Conformational Cycle of the ABC Transporter MsbA in Liposomes: Detailed Analysis Using Double Electron–Electron Resonance Spectroscopy Zou, Ping; Bortolus, Marco; Mchaourab, Hassane S. Journal of Molecular Biology, Vol. 393, Issue 3 https://doi.org/10.1016/j.jmb.2009.08.050	journal	October 2009
High-resolution distance mapping in rhodopsin reveals the pattern of helix movement due to activation Altenbach, C.; Kusnetzow, A. K.; Ernst, O. P. Proceedings of the National Academy of Sciences, Vol. 105, Issue 21 https://doi.org/10.1073/pnas.0802515105	journal	May 2008
The hydrophobic moment detects periodicity in protein hydrophobicity. Eisenberg, D.; Weiss, R. M.; Terwilliger, T. C. Proceedings of the National Academy of Sciences, Vol. 81, Issue 1 https://doi.org/10.1073/pnas.81.1.140	journal	January 1984

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