Constructing protein polyhedra via orthogonal chemical interactions
Abstract
Many proteins exist naturally as symmetrical homooligomers or homopolymers. The emergent structural and functional properties of such protein assemblies have inspired extensive efforts in biomolecular design2–5. As synthesized by ribosomes, proteins are inherently asymmetric. Therefore, they must acquire multiple surface patches that selectively associate to generate the different symmetry elements needed to form higher-order architectures—a daunting task for protein design. Here we address this problem using an inorganic chemical approach, whereby multiple modes of protein–protein interactions and symmetry are simultaneously achieved by selective, ‘one-pot’ coordination of soft and hard metal ions. We show that a monomeric protein (protomer) appropriately modified with biologically inspired hydroxamate groups and zinc-binding motifs assembles through concurrent Fe3+ and Zn2+ coordination into discrete dodecameric and hexameric cages. Our cages closely resemble natural polyhedral protein architectures and are, to our knowledge, unique among designed systems in that they possess tightly packed shells devoid of large apertures. At the same time, they can assemble and disassemble in response to diverse stimuli, owing to their heterobimetallic construction on minimal interprotein-bonding footprints. With stoichiometries ranging from [2 Fe:9 Zn:6 protomers] to [8 Fe:21 Zn:12 protomers], these protein cages represent some of the compositionally most complex protein assemblies—or inorganic coordination complexes—obtainedmore »
- Authors:
-
- Univ. of California, San Diego, CA (United States)
- Publication Date:
- Research Org.:
- Univ. of California, San Diego, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES). Materials Sciences & Engineering Division
- OSTI Identifier:
- 1594978
- Grant/Contract Number:
- SC0003844
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Nature (London)
- Additional Journal Information:
- Journal Name: Nature (London); Journal Volume: 578; Journal ID: ISSN 0028-0836
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 36 MATERIALS SCIENCE; 59 BASIC BIOLOGICAL SCIENCES; 77 NANOSCIENCE AND NANOTECHNOLOGY
Citation Formats
Golub, Eyal, Subramanian, Rohit H., Esselborn, Julian, Alberstein, Robert G., Bailey, Jake B., Chiong, Jerika A., Yan, Xiaodong, Booth, Timothy, Baker, Timothy S., and Tezcan, F. Akif. Constructing protein polyhedra via orthogonal chemical interactions. United States: N. p., 2020.
Web. doi:10.1038/s41586-019-1928-2.
Golub, Eyal, Subramanian, Rohit H., Esselborn, Julian, Alberstein, Robert G., Bailey, Jake B., Chiong, Jerika A., Yan, Xiaodong, Booth, Timothy, Baker, Timothy S., & Tezcan, F. Akif. Constructing protein polyhedra via orthogonal chemical interactions. United States. https://doi.org/10.1038/s41586-019-1928-2
Golub, Eyal, Subramanian, Rohit H., Esselborn, Julian, Alberstein, Robert G., Bailey, Jake B., Chiong, Jerika A., Yan, Xiaodong, Booth, Timothy, Baker, Timothy S., and Tezcan, F. Akif. Wed .
"Constructing protein polyhedra via orthogonal chemical interactions". United States. https://doi.org/10.1038/s41586-019-1928-2. https://www.osti.gov/servlets/purl/1594978.
@article{osti_1594978,
title = {Constructing protein polyhedra via orthogonal chemical interactions},
author = {Golub, Eyal and Subramanian, Rohit H. and Esselborn, Julian and Alberstein, Robert G. and Bailey, Jake B. and Chiong, Jerika A. and Yan, Xiaodong and Booth, Timothy and Baker, Timothy S. and Tezcan, F. Akif},
abstractNote = {Many proteins exist naturally as symmetrical homooligomers or homopolymers. The emergent structural and functional properties of such protein assemblies have inspired extensive efforts in biomolecular design2–5. As synthesized by ribosomes, proteins are inherently asymmetric. Therefore, they must acquire multiple surface patches that selectively associate to generate the different symmetry elements needed to form higher-order architectures—a daunting task for protein design. Here we address this problem using an inorganic chemical approach, whereby multiple modes of protein–protein interactions and symmetry are simultaneously achieved by selective, ‘one-pot’ coordination of soft and hard metal ions. We show that a monomeric protein (protomer) appropriately modified with biologically inspired hydroxamate groups and zinc-binding motifs assembles through concurrent Fe3+ and Zn2+ coordination into discrete dodecameric and hexameric cages. Our cages closely resemble natural polyhedral protein architectures and are, to our knowledge, unique among designed systems in that they possess tightly packed shells devoid of large apertures. At the same time, they can assemble and disassemble in response to diverse stimuli, owing to their heterobimetallic construction on minimal interprotein-bonding footprints. With stoichiometries ranging from [2 Fe:9 Zn:6 protomers] to [8 Fe:21 Zn:12 protomers], these protein cages represent some of the compositionally most complex protein assemblies—or inorganic coordination complexes—obtained by design.},
doi = {10.1038/s41586-019-1928-2},
journal = {Nature (London)},
number = ,
volume = 578,
place = {United States},
year = {Wed Jan 22 00:00:00 EST 2020},
month = {Wed Jan 22 00:00:00 EST 2020}
}
Free Publicly Available Full Text
Publisher's Version of Record
Other availability
Search WorldCat to find libraries that may hold this journal
Cited by: 78 works
Citation information provided by
Web of Science
Web of Science
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
Linking Crystallographic Model and Data Quality
journal, May 2012
- Karplus, P. A.; Diederichs, K.
- Science, Vol. 336, Issue 6084
Nanohedra: Using symmetry to design self assembling protein cages, layers, crystals, and filaments
journal, February 2001
- Padilla, J. E.; Colovos, C.; Yeates, T. O.
- Proceedings of the National Academy of Sciences, Vol. 98, Issue 5
Protein self-assembly via supramolecular strategies
journal, January 2016
- Bai, Yushi; Luo, Quan; Liu, Junqiu
- Chemical Society Reviews, Vol. 45, Issue 10
Oxidation-Reduction Potential of Ascorbic Acid (Vitamin C)
journal, September 1933
- Borsook, H.; Keighley, G.
- Proceedings of the National Academy of Sciences, Vol. 19, Issue 9
Structural Characterization of a Microperoxidase Inside a Metal-Directed Protein Cage
journal, August 2010
- Ni, Thomas W.; Tezcan, F. Akif
- Angewandte Chemie International Edition, Vol. 49, Issue 39
An efficient one-step site-directed deletion, insertion, single and multiple-site plasmid mutagenesis protocol
journal, January 2008
- Liu, Huanting; Naismith, James H.
- BMC Biotechnology, Vol. 8, Issue 1
Accurate design of megadalton-scale two-component icosahedral protein complexes
journal, July 2016
- Bale, J. B.; Gonen, S.; Liu, Y.
- Science, Vol. 353, Issue 6297
Acid Catalysis in Basic Solution: A Supramolecular Host Promotes Orthoformate Hydrolysis
journal, April 2007
- Pluth, M. D.; Bergman, R. G.; Raymond, K. N.
- Science, Vol. 316, Issue 5821
Structure, Dynamics, Assembly, and Evolution of Protein Complexes
journal, June 2015
- Marsh, Joseph A.; Teichmann, Sarah A.
- Annual Review of Biochemistry, Vol. 84, Issue 1
Quasi-equivalent viruses: a paradigm for protein assemblies 1 1Edited by T. Richmond
journal, July 1997
- Johnson, John E.; Speir, Jeffrey A.
- Journal of Molecular Biology, Vol. 269, Issue 5
A model for sedimentation in inhomogeneous media. I. Dynamic density gradients from sedimenting co-solutes
journal, March 2004
- Schuck, Peter
- Biophysical Chemistry, Vol. 108, Issue 1-3
New tools for automated high-resolution cryo-EM structure determination in RELION-3
journal, November 2018
- Zivanov, Jasenko; Nakane, Takanori; Forsberg, Björn O.
- eLife, Vol. 7
An ultra-stable gold-coordinated protein cage displaying reversible assembly
journal, May 2019
- Malay, Ali D.; Miyazaki, Naoyuki; Biela, Artur
- Nature, Vol. 569, Issue 7756
Metal-directed, chemically tunable assembly of one-, two- and three-dimensional crystalline protein arrays
journal, March 2012
- Brodin, Jeffrey D.; Ambroggio, X. I.; Tang, Chunyan
- Nature Chemistry, Vol. 4, Issue 5
MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy
journal, February 2017
- Zheng, Shawn Q.; Palovcak, Eugene; Armache, Jean-Paul
- Nature Methods, Vol. 14, Issue 4
Integration, scaling, space-group assignment and post-refinement
journal, January 2010
- Kabsch, Wolfgang
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 133-144
XDS
journal, January 2010
- Kabsch, Wolfgang
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2
Assembly, stability and dynamics of virus capsids
journal, March 2013
- Mateu, Mauricio G.
- Archives of Biochemistry and Biophysics, Vol. 531, Issue 1-2
UCSF Chimera?A visualization system for exploratory research and analysis
journal, January 2004
- Pettersen, Eric F.; Goddard, Thomas D.; Huang, Conrad C.
- Journal of Computational Chemistry, Vol. 25, Issue 13
Supramolecular Archimedean Cages Assembled with 72 Hydrogen Bonds
journal, July 2011
- Liu, Y.; Hu, C.; Comotti, A.
- Science, Vol. 333, Issue 6041, p. 436-440
Quantifying the local resolution of cryo-EM density maps
journal, November 2013
- Kucukelbir, Alp; Sigworth, Fred J.; Tagare, Hemant D.
- Nature Methods, Vol. 11, Issue 1
Self-Assembling Cages from Coiled-Coil Peptide Modules
journal, April 2013
- Fletcher, J. M.; Harniman, R. L.; Barnes, F. R. H.
- Science, Vol. 340, Issue 6132
The Redox Potential of Dithionite and SO-2 from Equilibrium Reactions with Flavodoxins, Methyl Viologen and Hydrogen plus Hydrogenase
journal, April 1978
- Mayhew, Stephen G.
- European Journal of Biochemistry, Vol. 85, Issue 2
Gctf: Real-time CTF determination and correction
journal, January 2016
- Zhang, Kai
- Journal of Structural Biology, Vol. 193, Issue 1
CalFitter: a web server for analysis of protein thermal denaturation data
journal, May 2018
- Mazurenko, Stanislav; Stourac, Jan; Kunka, Antonin
- Nucleic Acids Research, Vol. 46, Issue W1
Protein Assemblies: Nature-Inspired and Designed Nanostructures
journal, March 2019
- Hamley, Ian W.
- Biomacromolecules, Vol. 20, Issue 5
Modular and Versatile Hybrid Coordination Motifs on α-Helical Protein Surfaces
journal, August 2010
- Radford, Robert J.; Nguyen, Phuong C.; Tezcan, F. Akif
- Inorganic Chemistry, Vol. 49, Issue 15
Crystal Structures of Tris(hydroxamato) Complexes of Iron(III)
journal, January 2000
- Failes, Timothy W.; Hambley, Trevor W.
- Australian Journal of Chemistry, Vol. 53, Issue 10
MolProbity : all-atom structure validation for macromolecular crystallography
journal, December 2009
- Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J.
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1
White Phosphorus Is Air-Stable Within a Self-Assembled Tetrahedral Capsule
journal, June 2009
- Mal, P.; Breiner, B.; Rissanen, K.
- Science, Vol. 324, Issue 5935, p. 1697-1699
Rational Design and Assembly of M 2 M‘ 3 L 6 Supramolecular Clusters with C 3 h Symmetry by Exploiting Incommensurate Symmetry Numbers §
journal, March 2001
- Sun, Xiankai; Johnson, Darren W.; Caulder, Dana L.
- Journal of the American Chemical Society, Vol. 123, Issue 12
Features and development of Coot
journal, March 2010
- Emsley, P.; Lohkamp, B.; Scott, W. G.
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4
Coordination chemistry of microbial iron transport compounds. 24. Characterization of coprogen and ferricrocin, two ferric hydroxamate siderophores
journal, February 1983
- Wong, Geoffrey B.; Kappel, Mary J.; Raymond, Kenneth N.
- Journal of the American Chemical Society, Vol. 105, Issue 4
Solving the structure of human H ferritin by genetically engineering intermolecular crystal contacts
journal, February 1991
- Lawson, David M.; Artymiuk, Peter J.; Yewdall, Stephen J.
- Nature, Vol. 349, Issue 6309
Iron bioavailability and the coordination chemistry of hydroxamic acids
journal, November 1990
- Crumbliss, A.
- Coordination Chemistry Reviews, Vol. 105, Issue 1
UCSF ChimeraX: Meeting modern challenges in visualization and analysis: UCSF ChimeraX Visualization System
journal, September 2017
- Goddard, Thomas D.; Huang, Conrad C.; Meng, Elaine C.
- Protein Science, Vol. 27, Issue 1
PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010
- Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
Geometric Principles for Designing Highly Symmetric Self-Assembling Protein Nanomaterials
journal, May 2017
- Yeates, Todd O.
- Annual Review of Biophysics, Vol. 46, Issue 1
Die Kristall- und Molekülstruktur des Eisen(III)-benzhydroxamat-Trihydrates
journal, May 1969
- Lindner, H. J.; Göttlicher, S.
- Acta Crystallographica Section B Structural Crystallography and Crystal Chemistry, Vol. 25, Issue 5
Stability and Folding Kinetics of Structurally Characterized Cytochrome c - b 562 † , ‡
journal, September 2006
- Faraone-Mennella, Jasmin; Tezcan, F. Akif; Gray, Harry B.
- Biochemistry, Vol. 45, Issue 35
Supramolecular Coordination: Self-Assembly of Finite Two- and Three-Dimensional Ensembles
journal, November 2011
- Chakrabarty, Rajesh; Mukherjee, Partha Sarathi; Stang, Peter J.
- Chemical Reviews, Vol. 111, Issue 11, p. 6810-6918
Structure of a 16-nm Cage Designed by Using Protein Oligomers
journal, May 2012
- Lai, Y. -T.; Cascio, D.; Yeates, T. O.
- Science, Vol. 336, Issue 6085
Hard and Soft Acids and Bases
journal, November 1963
- Pearson, Ralph G.
- Journal of the American Chemical Society, Vol. 85, Issue 22
Functional Molecular Flasks: New Properties and Reactions within Discrete, Self-Assembled Hosts
journal, April 2009
- Yoshizawa, Michito; Klosterman, Jeremy K.; Fujita, Makoto
- Angewandte Chemie International Edition, Vol. 48, Issue 19, p. 3418-3438
Self-assembly of coherently dynamic, auxetic, two-dimensional protein crystals
journal, May 2016
- Suzuki, Yuta; Cardone, Giovanni; Restrepo, David
- Nature, Vol. 533, Issue 7603
Integrative Self-Sorting Synthesis of a Fe 8 Pt 6 L 24 Cubic Cage
journal, June 2012
- Smulders, Maarten M. J.; Jiménez, Azucena; Nitschke, Jonathan R.
- Angewandte Chemie International Edition, Vol. 51, Issue 27
Studies towards dynamic kinetic resolution of 4-hydroxy-2-methylcyclopent-2-en-1-one and its E - O -trityloxime
journal, August 2016
- Michalak, Karol; Wicha, Jerzy; Wójcik, Jacek
- Tetrahedron, Vol. 72, Issue 32
Design and Construction of Functional Supramolecular Metalloprotein Assemblies
journal, January 2019
- Churchfield, Lewis A.; Tezcan, F. Akif
- Accounts of Chemical Research, Vol. 52, Issue 2
Structural Characterization of a Microperoxidase Inside a Metal-Directed Protein Cage
journal, August 2010
- Ni, Thomas W.; Tezcan, F. Akif
- Angewandte Chemie, Vol. 122, Issue 39
Exploring the gas access routes in a [NiFeSe] hydrogenase using crystals pressurized with krypton and oxygen
journal, August 2020
- Zacarias, Sónia; Temporão, Adriana; Carpentier, Philippe
- JBIC Journal of Biological Inorganic Chemistry, Vol. 25, Issue 6
PARP1 exhibits enhanced association and catalytic efficiency with γH2A.X-nucleosome
journal, December 2019
- Sharma, Deepti; De Falco, Louis; Padavattan, Sivaraman
- Nature Communications, Vol. 10, Issue 1
Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation
journal, February 2021
- Tillu, Vikas A.; Rae, James; Gao, Ya
- Nature Communications, Vol. 12, Issue 1
PHENIX: a comprehensive Python-based system for macromolecular structure solution.
text, January 2010
- Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
- Apollo - University of Cambridge Repository