Principles for designing proteins with cavities formed by curved β sheets

Marcos, Enrique; Basanta, Benjamin; Chidyausiku, Tamuka M.; Tang, Yuefeng; Oberdorfer, Gustav; Liu, Gaohua; Swapna, G. V.  T.; Guan, Rongjin; Silva, Daniel-Adriano; Dou, Jiayi; Pereira, Jose Henrique; Xiao, Rong; Sankaran, Banumathi; Zwart, Peter H.; Montelione, Gaetano T.; Baker, David

doi:10.1126/science.aah7389

Title: Principles for designing proteins with cavities formed by curved β sheets

Journal Article · Thu Jan 12 00:00:00 EST 2017 · Science

DOI:https://doi.org/10.1126/science.aah7389· OSTI ID:1409590

Marcos, Enrique; Basanta, Benjamin; Chidyausiku, Tamuka M.; Tang, Yuefeng; Oberdorfer, Gustav; Liu, Gaohua; Swapna, G. V. T.; Guan, Rongjin; Silva, Daniel-Adriano; Dou, Jiayi; Pereira, Jose Henrique; Xiao, Rong; Sankaran, Banumathi; Zwart, Peter H.; Montelione, Gaetano T.; Baker, David

Active sites and ligand-binding cavities in native proteins are often formed by curved β sheets, and the ability to control β-sheet curvature would allow design of binding proteins with cavities customized to specific ligands. Toward this end, we investigated the mechanisms controlling β-sheet curvature by studying the geometry of β sheets in naturally occurring protein structures and folding simulations. The principles emerging from this analysis were used to design, de novo, a series of proteins with curved β sheets topped with α helices. Nuclear magnetic resonance and crystal structures of the designs closely match the computational models, showing that β-sheet curvature can be controlled with atomic-level accuracy. Our approach enables the design of proteins with cavities and provides a route to custom design ligand-binding and catalytic sites.

Cite

Export

Save

Research Organization:: Brookhaven National Laboratory (BNL), Upton, NY (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

DOE Contract Number:: SC0012704

OSTI ID:: 1409590

Report Number(s):: BNL-114642-2017-JA¿¿¿

Journal Information:: Science, Vol. 355, Issue 6321; ISSN 0036-8075

Publisher:: AAAS

Country of Publication:: United States

Language:: English

References (58)

Combined Covalent-Electrostatic Model of Hydrogen Bonding Improves Structure Prediction with Rosetta O’Meara, Matthew J.; Leaver-Fay, Andrew; Tyka, Michael D. Journal of Chemical Theory and Computation, Vol. 11, Issue 2 https://doi.org/10.1021/ct500864r	journal	January 2015
Kemp elimination catalysts by computational enzyme design Röthlisberger, Daniela; Khersonsky, Olga; Wollacott, Andrew M. Nature, Vol. 453, Issue 7192, p. 190-195 https://doi.org/10.1038/nature06879	journal	March 2008
TM-align: a protein structure alignment algorithm based on the TM-score Zhang, Y. Nucleic Acids Research, Vol. 33, Issue 7 https://doi.org/10.1093/nar/gki524	journal	April 2005
Exploring the repeat protein universe through computational protein design Brunette, Tj; Parmeggiani, Fabio; Huang, Po-Ssu Nature, Vol. 528, Issue 7583 https://doi.org/10.1038/nature16162	journal	December 2015
Identification, classification, and analysis of beta-bulges in proteins Chan, A. W. Edith; Hutchinson, E. Gail; Harris, Daniel Protein Science, Vol. 2, Issue 10 https://doi.org/10.1002/pro.5560021004	journal	October 1993
High-level production of uniformly 15N-and 13C-enriched fusion proteins in Escherichia coli Jansson, Magnus; Li, Yu-Chin; Jendeberg, Lena Journal of Biomolecular NMR, Vol. 7, Issue 2 https://doi.org/10.1007/BF00203823	journal	March 1996
Design of activated serine–containing catalytic triads with atomic-level accuracy Rajagopalan, Sridharan; Wang, Chu; Yu, Kai Nature Chemical Biology, Vol. 10, Issue 5 https://doi.org/10.1038/nchembio.1498	journal	April 2014
PISCES: a protein sequence culling server Wang, G.; Dunbrack, R. L. Bioinformatics, Vol. 19, Issue 12 https://doi.org/10.1093/bioinformatics/btg224	journal	August 2003
NMR data collection and analysis protocol for high-throughput protein structure determination Liu, G.; Shen, Y.; Atreya, H. S. Proceedings of the National Academy of Sciences, Vol. 102, Issue 30 https://doi.org/10.1073/pnas.0504338102	journal	July 2005
The high-throughput protein sample production platform of the Northeast Structural Genomics Consortium Xiao, Rong; Anderson, Stephen; Aramini, James Journal of Structural Biology, Vol. 172, Issue 1 https://doi.org/10.1016/j.jsb.2010.07.011	journal	October 2010
De novo design of a four-fold symmetric TIM-barrel protein with atomic-level accuracy Huang, Po-Ssu; Feldmeier, Kaspar; Parmeggiani, Fabio Nature Chemical Biology, Vol. 12, Issue 1 https://doi.org/10.1038/nchembio.1966	journal	November 2015
High thermodynamic stability of parametrically designed helical bundles Huang, Po-Ssu; Oberdorfer, Gustav; Xu, Chunfu Science, Vol. 346, Issue 6208 https://doi.org/10.1126/science.1257481	journal	October 2014
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs Altschul, Stephen F.; Madden, Thomas L.; Schäffer, Alejandro A. Nucleic Acids Research, Vol. 25, Issue 17, p. 3389-3402 https://doi.org/10.1093/nar/25.17.3389	journal	September 1997
PDBStat: a universal restraint converter and restraint analysis software package for protein NMR Tejero, Roberto; Snyder, David; Mao, Binchen Journal of Biomolecular NMR, Vol. 56, Issue 4 https://doi.org/10.1007/s10858-013-9753-7	journal	July 2013
Toward High-Resolution de Novo Structure Prediction for Small Proteins Bradley, P. Science, Vol. 309, Issue 5742 https://doi.org/10.1126/science.1113801	journal	September 2005
Evaluating protein structures determined by structural genomics consortia Bhattacharya, Aneerban; Tejero, Roberto; Montelione, Gaetano T. Proteins: Structure, Function, and Bioinformatics, Vol. 66, Issue 4 https://doi.org/10.1002/prot.21165	journal	December 2006
Computational design of ligand-binding proteins with high affinity and selectivity Tinberg, Christine E.; Khare, Sagar D.; Dou, Jiayi Nature, Vol. 501, Issue 7466, p. 212-216 https://doi.org/10.1038/nature12443	journal	September 2013
The solution structure of eglin c based on measurements of many NOEs and coupling constants and its comparison with X‐ray structures Hyberts, Sven G.; Goldberg, Matthew S.; Havel, Timothy F. Protein Science, Vol. 1, Issue 6 https://doi.org/10.1002/pro.5560010606	journal	June 1992
Computational design of water-soluble α-helical barrels Thomson, Andrew R.; Wood, Christopher W.; Burton, Antony J. Science, Vol. 346, Issue 6208 https://doi.org/10.1126/science.1257452	journal	October 2014
UCSF Chimera?A visualization system for exploratory research and analysis Pettersen, Eric F.; Goddard, Thomas D.; Huang, Conrad C. Journal of Computational Chemistry, Vol. 25, Issue 13 https://doi.org/10.1002/jcc.20084	journal	January 2004
Design of a Novel Globular Protein Fold with Atomic-Level Accuracy Kuhlman, Brian; Dantas, Gautam; Ireton, Gregory C. Science, Vol. 302, Issue 5649 https://doi.org/10.1126/science.1089427	journal	November 2003
Computational Design of Catalytic Dyads and Oxyanion Holes for Ester Hydrolysis Richter, Florian; Blomberg, Rebecca; Khare, Sagar D. Journal of the American Chemical Society, Vol. 134, Issue 39 https://doi.org/10.1021/ja3037367	journal	September 2012
Protein Structure Prediction Using Rosetta Rohl, Carol A.; Strauss, Charlie E. M.; Misura, Kira M. S. Methods in Enzymology https://doi.org/10.1016/S0076-6879(04)83004-0	book	January 2004
Control over overall shape and size in de novo designed proteins Lin, Yu-Ru; Koga, Nobuyasu; Tatsumi-Koga, Rie Proceedings of the National Academy of Sciences, Vol. 112, Issue 40 https://doi.org/10.1073/pnas.1509508112	journal	September 2015
Natural -sheet proteins use negative design to avoid edge-to-edge aggregation Richardson, J. S.; Richardson, D. C. Proceedings of the National Academy of Sciences, Vol. 99, Issue 5 https://doi.org/10.1073/pnas.052706099	journal	March 2002
Principles for designing ideal protein structures Koga, Nobuyasu; Tatsumi-Koga, Rie; Liu, Gaohua Nature, Vol. 491, Issue 7423 https://doi.org/10.1038/nature11600	journal	November 2012
Evolution of a designed retro-aldolase leads to complete active site remodeling Giger, Lars; Caner, Sami; Obexer, Richard Nature Chemical Biology, Vol. 9, Issue 8 https://doi.org/10.1038/nchembio.1276	journal	June 2013
Coot model-building tools for molecular graphics Emsley, Paul; Cowtan, Kevin Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132 https://doi.org/10.1107/S0907444904019158	journal	November 2004
Comparisons of NMR Spectral Quality and Success in Crystallization Demonstrate that NMR and X-ray Crystallography Are Complementary Methods for Small Protein Structure Determination Snyder, David A.; Chen, Yang; Denissova, Natalia G. Journal of the American Chemical Society, Vol. 127, Issue 47 https://doi.org/10.1021/ja053564h	journal	November 2005
The beta bulge: a common small unit of nonrepetitive protein structure. Richardson, J. S.; Getzoff, E. D.; Richardson, D. C. Proceedings of the National Academy of Sciences, Vol. 75, Issue 6 https://doi.org/10.1073/pnas.75.6.2574	journal	June 1978
Dictionary of protein secondary structure: Pattern recognition of hydrogen-bonded and geometrical features Kabsch, Wolfgang; Sander, Christian Biopolymers, Vol. 22, Issue 12 https://doi.org/10.1002/bip.360221211	journal	December 1983
Protein NMR Recall, Precision, and F -measure Scores (RPF Scores): Structure Quality Assessment Measures Based on Information Retrieval Statistics Huang, Yuanpeng J.; Powers, Robert; Montelione, Gaetano T. Journal of the American Chemical Society, Vol. 127, Issue 6 https://doi.org/10.1021/ja047109h	journal	February 2005
Native protein sequences are close to optimal for their structures Kuhlman, B.; Baker, D. Proceedings of the National Academy of Sciences, Vol. 97, Issue 19 https://doi.org/10.1073/pnas.97.19.10383	journal	September 2000
BLAST+: architecture and applications Camacho, Christiam; Coulouris, George; Avagyan, Vahram BMC Bioinformatics, Vol. 10, Issue 1 https://doi.org/10.1186/1471-2105-10-421	journal	January 2009
BPPred: A Web-based computational tool for predicting biophysical parameters of proteins Geierhaas, C. D.; Nickson, A. A.; Lindorff-Larsen, K. Protein Science, Vol. 16, Issue 1 https://doi.org/10.1110/ps.062383807	journal	November 2006
PHENIX: a comprehensive Python-based system for macromolecular structure solution Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221 https://doi.org/10.1107/S0907444909052925	journal	January 2010
Computational Design of an Enzyme Catalyst for a Stereoselective Bimolecular Diels-Alder Reaction Siegel, J. B.; Zanghellini, A.; Lovick, H. M. Science, Vol. 329, Issue 5989 https://doi.org/10.1126/science.1190239	journal	July 2010
Rational design of α-helical tandem repeat proteins with closed architectures Doyle, Lindsey; Hallinan, Jazmine; Bolduc, Jill Nature, Vol. 528, Issue 7583 https://doi.org/10.1038/nature16191	journal	December 2015
RosettaHoles2: A volumetric packing measure for protein structure refinement and validation: RosettaHoles2 for Protein Structure Sheffler, William; Baker, David Protein Science, Vol. 19, Issue 10 https://doi.org/10.1002/pro.458	journal	July 2010
De novo design of a transmembrane Zn ²⁺ -transporting four-helix bundle Joh, Nathan H.; Wang, Tuo; Bhate, Manasi P. Science, Vol. 346, Issue 6216 https://doi.org/10.1126/science.1261172	journal	December 2014
De Novo Computational Design of Retro-Aldol Enzymes Jiang, L.; Althoff, E. A.; Clemente, F. R. Science, Vol. 319, Issue 5868 https://doi.org/10.1126/science.1152692	journal	March 2008
Design of structurally distinct proteins using strategies inspired by evolution Jacobs, T. M.; Williams, B.; Williams, T. Science, Vol. 352, Issue 6286 https://doi.org/10.1126/science.aad8036	journal	May 2016
Automatic Classification and Analysis of αα-Turn Motifs in Proteins Wintjens, René T.; Rooman, Marianne J.; Wodak, Shoshana J. Journal of Molecular Biology, Vol. 255, Issue 1 https://doi.org/10.1006/jmbi.1996.0020	journal	January 1996
Structural properties of protein β-sheets Salemme, F. R. Progress in Biophysics and Molecular Biology, Vol. 42 https://doi.org/10.1016/0079-6107(83)90005-6	journal	January 1983
Stereospecific nuclear magnetic resonance assignments of the methyl groups of valine and leucine in the DNA-binding domain of the 434 repressor by biosynthetically directed fractional carbon-13 labeling Neri, Dario; Szyperski, Thomas; Otting, Gottfried Biochemistry, Vol. 28, Issue 19 https://doi.org/10.1021/bi00445a003	journal	September 1989
Rosetta3: An Object-Oriented Software Suite for the Simulation and Design of Macromolecules Leaver-Fay, Andrew; Tyka, Michael; Lewis, Steven M. Computer Methods, Part C https://doi.org/10.1016/B978-0-12-381270-4.00019-6	book	January 2011
Installing hydrolytic activity into a completely de novo protein framework Burton, Antony J.; Thomson, Andrew R.; Dawson, William M. Nature Chemistry, Vol. 8, Issue 9 https://doi.org/10.1038/nchem.2555	journal	July 2016
RosettaScripts: A Scripting Language Interface to the Rosetta Macromolecular Modeling Suite Fleishman, Sarel J.; Leaver-Fay, Andrew; Corn, Jacob E. PLoS ONE, Vol. 6, Issue 6 https://doi.org/10.1371/journal.pone.0020161	journal	June 2011
3V: cavity, channel and cleft volume calculator and extractor Voss, N. R.; Gerstein, M. Nucleic Acids Research, Vol. 38, Issue Web Server https://doi.org/10.1093/nar/gkq395	journal	May 2010
Computational design of self-assembling cyclic protein homo-oligomers Fallas, Jorge A.; Ueda, George; Sheffler, William Nature Chemistry, Vol. 9, Issue 4 https://doi.org/10.1038/nchem.2673	journal	December 2016
COFACTOR: an accurate comparative algorithm for structure-based protein function annotation Roy, Ambrish; Yang, Jianyi; Zhang, Yang Nucleic Acids Research, Vol. 40, Issue W1 https://doi.org/10.1093/nar/gks372	journal	May 2012
The origin of β-strand bending in globular proteins Fujiwara, Kazuo; Ebisawa, Shinichi; Watanabe, Yuka BMC Structural Biology, Vol. 15, Issue 1 https://doi.org/10.1186/s12900-015-0048-y	journal	October 2015
A deliberate approach to screening for initial crystallization conditions of biological macromolecules Luft, Joseph R.; Collins, Robert J.; Fehrman, Nancy A. Journal of Structural Biology, Vol. 142, Issue 1 https://doi.org/10.1016/S1047-8477(03)00048-0	journal	April 2003
Automated Structure Solution with the PHENIX Suite Zwart, Peter H.; Afonine, Pavel V.; Grosse-Kunstleve, Ralf W. Methods in Molecular Biology https://doi.org/10.1007/978-1-60327-058-8_28	book	January 2008
A test of the linear extrapolation of unfolding free energy changes over an extended denaturant concentration range Santoro, Marcelo M.; Bolen, D. W. Biochemistry, Vol. 31, Issue 20 https://doi.org/10.1021/bi00135a022	journal	May 1992
Phaser crystallographic software McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Journal of Applied Crystallography, Vol. 40, Issue 4 https://doi.org/10.1107/S0021889807021206	journal	July 2007
Protein secondary structure prediction based on position-specific scoring matrices 1 1Edited by G. Von Heijne Jones, David T. Journal of Molecular Biology, Vol. 292, Issue 2 https://doi.org/10.1006/jmbi.1999.3091	journal	September 1999
A microscale protein NMR sample screening pipeline Rossi, Paolo; Swapna, G. V. T.; Huang, Yuanpeng J. Journal of Biomolecular NMR, Vol. 46, Issue 1 https://doi.org/10.1007/s10858-009-9386-z	journal	November 2009

Similar Records

De novo design of a fluorescence-activating β-barrel

Journal Article · Wed Sep 12 00:00:00 EDT 2018 · Nature (London) · OSTI ID:1409590

Dou, Jiayi; Vorobieva, Anastassia A.; Sheffler, William; +15 more

β-sheet-like formation during the mechanical unfolding of prion protein

Journal Article · Mon Sep 28 00:00:00 EDT 2015 · Journal of Chemical Physics · OSTI ID:1409590

Tao, Weiwei; Cao, Penghui; Yoon, Gwonchan; +1 more

Intermediate conformation between native β-sheet and non-native α-helix is a precursor of trifluoroethanol-induced aggregation of Human Carbonic Anhydrase-II

Journal Article · Fri Jun 20 00:00:00 EDT 2014 · Biochemical and Biophysical Research Communications · OSTI ID:1409590

Gupta, Preeti; Deep, Shashank

Related Subjects

59 BASIC BIOLOGICAL SCIENCES

Title: Principles for designing proteins with cavities formed by curved β sheets

Citation Formats

References (58)

Similar Records

Related Subjects