Design of light- and chemically responsive protein assemblies through host-guest interactions

Zhang, Zhiyin; Chiang, Huat T.; Xia, Ying; Avakyan, Nicole; Sonani, Ravi R.; Wang, Fengbin; Egelman, Edward H.; De Yoreo, James J.; Pozzo, Lilo D.; Tezcan, F. Akif

doi:10.1016/j.chempr.2024.102407

Design of light- and chemically responsive protein assemblies through host-guest interactions

Journal Article · Mon Feb 10 00:00:00 UTC 2025 · Chem

DOI:https://doi.org/10.1016/j.chempr.2024.102407· OSTI ID:2558143

Zhang, Zhiyin ^[1]; Chiang, Huat T. ^[2]; Xia, Ying ^[2]; Avakyan, Nicole ^[1]; Sonani, Ravi R. ^[3]; Wang, Fengbin ^[4]; Egelman, Edward H. ^[3]; De Yoreo, James J. ^[5]; Pozzo, Lilo D. ^[2]; Tezcan, F. Akif ^[1]

Univ. of California, San Diego, CA (United States)
Univ. of Washington, Seattle, WA (United States)
Univ. of Virginia, Charlottesville, VA (United States)
Univ. of Virginia, Charlottesville, VA (United States); Univ. of Alabama, Birmingham, AL (United States)
Univ. of Washington, Seattle, WA (United States); Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Host-guest (HG) interactions have been widely used to build responsive materials and molecular machines owing to their inherently dynamic nature, interaction specificity, and responsiveness to diverse stimuli. Here, in this work, we have set out to exploit these advantages of HG chemistry in the design of dynamic protein assemblies, using a C₄ symmetric protein, ^C98RhuA, as a building block. We show that a ^C98RhuA variant individually modified with β-cyclodextrin (βCD) (host) or azobenzene (guest) functionalities can specifically pair with each other to form highly ordered 1D and 2D assemblies. Association and dissociation of ^βCDRhuA-^azoRhuA assemblies can be controlled by UV and visible light as well as by small-molecule modulators of βCD-azobenzene interactions. Kinetics analyses reveal that ^βCDRhuA-^azoRhuA nanotubes assemble without a nucleation barrier, a highly unusual occurrence for helical supramolecular systems. Taken together, our findings provide a compelling example for achieving complex structural and dynamic outcomes in protein assembly through simple chemical design.

View Accepted Manuscript (DOE)

Research Organization:: Univ. of Washington, Seattle, WA (United States)

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

Grant/Contract Number:: SC0003844; SC0019288

OSTI ID:: 2558143

Alternate ID(s):: OSTI ID: 3031181

Journal Information:: Chem, Journal Name: Chem Journal Issue: 6 Vol. 11; ISSN 2451-9294

Publisher:: Cell PressCopyright Statement

Country of Publication:: United States

Language:: English

References (69)

Self-Assembly of One- and Two-Dimensional Hemoprotein Systems by Polymerization through Heme-Heme Pocket Interactions Kitagishi, Hiroaki; Kakikura, Yasuaki; Yamaguchi, Hiroyasu Angewandte Chemie International Edition, Vol. 48, Issue 7 https://doi.org/10.1002/anie.200804006	journal	December 2008
Protein Dimerization Induced by Supramolecular Interactions with Cucurbit[8]uril Nguyen, Hoang D.; Dang, Dung T.; van Dongen, Joost L. J. Angewandte Chemie International Edition, Vol. 49, Issue 5 https://doi.org/10.1002/anie.200904413	journal	December 2009
Light-Responsive Capture and Release of DNA in a Ternary Supramolecular Complex Nalluri, Siva Krishna Mohan; Voskuhl, Jens; Bultema, Jelle B. Angewandte Chemie International Edition, Vol. 50, Issue 41 https://doi.org/10.1002/anie.201103707	journal	September 2011
Construction of Protein Nanowires through Cucurbit[8]uril-based Highly Specific Host-Guest Interactions: An Approach to the Assembly of Functional Proteins Hou, Chunxi; Li, Jiaxi; Zhao, Linlu Angewandte Chemie International Edition, Vol. 52, Issue 21 https://doi.org/10.1002/anie.201300692	journal	April 2013
An Antitumor Dual‐Responsive Host‐Guest Supramolecular Polymer Based on Hypoxia‐Cleavable Azocalix[4]arene Yao, Shun‐Yu; Yue, Yu‐Xin; Ying, An‐Kang Angewandte Chemie International Edition, Vol. 62, Issue 2 https://doi.org/10.1002/anie.202213578	journal	December 2022
Modulation of Protein Dimerization by a Supramolecular Host–Guest System Uhlenheuer, Dana A.; Wasserberg, Dorothee; Nguyen, Hoang Chemistry – A European Journal, Vol. 15, Issue 35 https://doi.org/10.1002/chem.200900462	journal	September 2009
Cucurbituril As A Versatile Tool to Tune the Functions of Proteins Hou, Chunxi; Zeng, Xiangzhi; Gao, Yuzhou Israel Journal of Chemistry, Vol. 58, Issue 3-4 https://doi.org/10.1002/ijch.201700105	journal	December 2017
Metal‐dependent assembly of a protein nano‐cage Cristie‐David, Ajitha S.; Marsh, E. Neil G. Protein Science https://doi.org/10.1002/pro.3676	journal	August 2019
Towards functional de novo designed proteins Dawson, William M.; Rhys, Guto G.; Woolfson, Derek N. Current Opinion in Chemical Biology, Vol. 52 https://doi.org/10.1016/j.cbpa.2019.06.011	journal	October 2019
Role of the Biomolecular Energy Gap in Protein Design, Structure, and Evolution Fleishman, Sarel J.; Baker, David Cell, Vol. 149, Issue 2 https://doi.org/10.1016/j.cell.2012.03.016	journal	April 2012
Structure and gating mechanism of the α7 nicotinic acetylcholine receptor Noviello, Colleen M.; Gharpure, Anant; Mukhtasimova, Nuriya Cell, Vol. 184, Issue 8 https://doi.org/10.1016/j.cell.2021.02.049	journal	April 2021
The Mechanism of Tubulin Assembly into Microtubules: Insights from Structural Studies Knossow, Marcel; Campanacci, Valérie; Khodja, Liza Ammar iScience, Vol. 23, Issue 9 https://doi.org/10.1016/j.isci.2020.101511	journal	September 2020
Structural Mechanisms of Peptide Recognition and Allosteric Modulation of Gene Regulation by the RRNPP Family of Quorum-Sensing Regulators Do, Hackwon; Kumaraswami, Muthiah Journal of Molecular Biology, Vol. 428, Issue 14 https://doi.org/10.1016/j.jmb.2016.05.026	journal	July 2016
Transient Protein-Protein Interactions: Structural, Functional, and Network Properties Perkins, James R.; Diboun, Ilhem; Dessailly, Benoit H. Structure, Vol. 18, Issue 10 https://doi.org/10.1016/j.str.2010.08.007	journal	October 2010
Protein Assembly by Design Zhu, Jie; Avakyan, Nicole; Kakkis, Albert Chemical Reviews, Vol. 121, Issue 22 https://doi.org/10.1021/acs.chemrev.1c00308	journal	August 2021
Artificial Molecular Machines Erbas-Cakmak, Sundus; Leigh, David A.; McTernan, Charlie T. Chemical Reviews, Vol. 115, Issue 18 https://doi.org/10.1021/acs.chemrev.5b00146	journal	August 2015
Functional Supramolecular Polymeric Networks: The Marriage of Covalent Polymers and Macrocycle-Based Host–Guest Interactions Xia, Danyu; Wang, Pi; Ji, Xiaofan Chemical Reviews, Vol. 120, Issue 13 https://doi.org/10.1021/acs.chemrev.9b00839	journal	May 2020
Ultralarge Single-Layer Porous Protein Nanosheet for Precise Nanosize Separation Zhang, Shenxiang; Zhang, Jianting; Fang, Wangxi Nano Letters, Vol. 18, Issue 10 https://doi.org/10.1021/acs.nanolett.8b03155	journal	September 2018
Fragmentation and Coagulation in Supramolecular (Co)polymerization Kinetics Markvoort, Albert J.; ten Eikelder, Huub M. M.; Hilbers, Peter A. J. ACS Central Science, Vol. 2, Issue 4 https://doi.org/10.1021/acscentsci.6b00009	journal	March 2016
Supramolecular Polymers Constructed from Macrocycle-Based Host–Guest Molecular Recognition Motifs Dong, Shengyi; Zheng, Bo; Wang, Feng Accounts of Chemical Research, Vol. 47, Issue 7 https://doi.org/10.1021/ar5000456	journal	March 2014
Cyclodextrin-Based Host–Guest Supramolecular Nanoparticles for Delivery: From Design to Applications Hu, Qi-Da; Tang, Gu-Ping; Chu, Paul K. Accounts of Chemical Research, Vol. 47, Issue 7 https://doi.org/10.1021/ar500055s	journal	April 2014
Photoresponsive Host–Guest Functional Systems Qu, Da-Hui; Wang, Qiao-Chun; Zhang, Qi-Wei Chemical Reviews, Vol. 115, Issue 15 https://doi.org/10.1021/cr5006342	journal	February 2015
Photoreconfigurable Supramolecular Nanotube Sendai, Toshihiro; Biswas, Shuvendu; Aida, Takuzo Journal of the American Chemical Society, Vol. 135, Issue 31 https://doi.org/10.1021/ja4060146	journal	July 2013
SpyAvidin Hubs Enable Precise and Ultrastable Orthogonal Nanoassembly Fairhead, Michael; Veggiani, Gianluca; Lever, Melissa Journal of the American Chemical Society, Vol. 136, Issue 35 https://doi.org/10.1021/ja505584f	journal	August 2014
Arylazopyrazoles as Light-Responsive Molecular Switches in Cyclodextrin-Based Supramolecular Systems Stricker, Lucas; Fritz, Eva-Corinna; Peterlechner, Martin Journal of the American Chemical Society, Vol. 138, Issue 13 https://doi.org/10.1021/jacs.6b00484	journal	March 2016
Determining the Structural and Energetic Basis of Allostery in a De Novo Designed Metalloprotein Assembly Churchfield, Lewis A.; Alberstein, Robert G.; Williamson, Laura M. Journal of the American Chemical Society, Vol. 140, Issue 31 https://doi.org/10.1021/jacs.8b05812	journal	July 2018
Chemically Controlled Helical Polymorphism in Protein Tubes by Selective Modulation of Supramolecular Interactions Li, Zhen; Chen, Shuyu; Gao, Chendi Journal of the American Chemical Society, Vol. 141, Issue 49 https://doi.org/10.1021/jacs.9b10505	journal	November 2019
Quasi-planar nucleus structure in apoferritin crystallization Yau, S. -T.; Vekilov, Peter G. Nature, Vol. 406, Issue 6795 https://doi.org/10.1038/35020035	journal	August 2000
The open pore conformation of potassium channels Jiang, Youxing; Lee, Alice; Chen, Jiayun Nature, Vol. 417, Issue 6888 https://doi.org/10.1038/417523a	journal	May 2002
The nature of the globular- to fibrous-actin transition Oda, Toshiro; Iwasa, Mitsusada; Aihara, Tomoki Nature, Vol. 457, Issue 7228 https://doi.org/10.1038/nature07685	journal	January 2009
Self-assembly of coherently dynamic, auxetic, two-dimensional protein crystals Suzuki, Yuta; Cardone, Giovanni; Restrepo, David Nature, Vol. 533, Issue 7603 https://doi.org/10.1038/nature17633	journal	May 2016
Metal-directed, chemically tunable assembly of one-, two- and three-dimensional crystalline protein arrays Brodin, Jeffrey D.; Ambroggio, X. I.; Tang, Chunyan Nature Chemistry, Vol. 4, Issue 5 https://doi.org/10.1038/nchem.1290	journal	March 2012
Biomolecular robotics for chemomechanically driven guest delivery fuelled by intracellular ATP Biswas, Shuvendu; Kinbara, Kazushi; Niwa, Tatsuya Nature Chemistry, Vol. 5, Issue 7 https://doi.org/10.1038/nchem.1681	journal	June 2013
Allosteric regulation and catalysis emerge via a common route Goodey, Nina M.; Benkovic, Stephen J. Nature Chemical Biology, Vol. 4, Issue 8 https://doi.org/10.1038/nchembio.98	journal	July 2008
Photoswitchable gel assembly based on molecular recognition Yamaguchi, Hiroyasu; Kobayashi, Yuichiro; Kobayashi, Ryosuke Nature Communications, Vol. 3, Issue 1 https://doi.org/10.1038/ncomms1617	journal	January 2012
Orthogonal switching of a single supramolecular complex Tian, Feng; Jiao, Dezhi; Biedermann, Frank Nature Communications, Vol. 3, Issue 1 https://doi.org/10.1038/ncomms2198	journal	November 2012
The unusual dynamics of parasite actin result from isodesmic polymerization Skillman, Kristen M.; Ma, Christopher I.; Fremont, Daved H. Nature Communications, Vol. 4, Issue 1 https://doi.org/10.1038/ncomms3285	journal	August 2013
Engineering the entropy-driven free-energy landscape of a dynamic nanoporous protein assembly Alberstein, Robert; Suzuki, Yuta; Paesani, Francesco Nature Chemistry, Vol. 10, Issue 7 https://doi.org/10.1038/s41557-018-0053-4	journal	April 2018
An ultra-stable gold-coordinated protein cage displaying reversible assembly Malay, Ali D.; Miyazaki, Naoyuki; Biela, Artur Nature, Vol. 569, Issue 7756 https://doi.org/10.1038/s41586-019-1185-4	journal	May 2019
Constructing protein polyhedra via orthogonal chemical interactions Golub, Eyal; Subramanian, Rohit H.; Esselborn, Julian Nature, Vol. 578, Issue 7793 https://doi.org/10.1038/s41586-019-1928-2	journal	January 2020
De novo protein design by deep network hallucination Anishchenko, Ivan; Pellock, Samuel J.; Chidyausiku, Tamuka M. Nature, Vol. 600, Issue 7889 https://doi.org/10.1038/s41586-021-04184-w	journal	December 2021
De novo design of protein structure and function with RFdiffusion Watson, Joseph L.; Juergens, David; Bennett, Nathaniel R. Nature, Vol. 620, Issue 7976 https://doi.org/10.1038/s41586-023-06415-8	journal	July 2023
Nucleation–elongation: a mechanism for cooperative supramolecular polymerization Zhao, Dahui; Moore, Jeffrey S. Org. Biomol. Chem., Vol. 1, Issue 20 https://doi.org/10.1039/B308788C	journal	January 2003
Assembly behavior of inclusion complexes of β-cyclodextrin with 4-hydroxyazobenzene and 4-aminoazobenzene Liu, Yu; Zhao, Yan-Li; Chen, Yong Org. Biomol. Chem., Vol. 3, Issue 4 https://doi.org/10.1039/B415946B	journal	January 2005
Charge-transfer interactions for the fabrication of multifunctional viral nanoparticles Hu, Jun; Wang, Peiyi; Zhao, Xia Chem. Commun., Vol. 50, Issue 91 https://doi.org/10.1039/C4CC05195E	journal	January 2014
Natural supramolecular protein assemblies Pieters, Bas J. G. E.; van Eldijk, Mark B.; Nolte, Roeland J. M. Chemical Society Reviews, Vol. 45, Issue 1 https://doi.org/10.1039/C5CS00157A	journal	January 2016
Construction of protein assemblies by host–guest interactions with cucurbiturils Hou, Chunxi; Huang, Zupeng; Fang, Yu Organic & Biomolecular Chemistry, Vol. 15, Issue 20 https://doi.org/10.1039/C7OB00686A	journal	January 2017
Disulfide-mediated reversible two-dimensional self-assembly of protein nanocages Zhou, K.; Chen, H.; Zhang, S. Chemical Communications, Vol. 55, Issue 52 https://doi.org/10.1039/C9CC03085A	journal	January 2019
Engineered assembly of a protein–cucurbituril biohybrid Guagnini, Francesca; Engilberge, Sylvain; Ramberg, Kiefer O. Chemical Communications, Vol. 56, Issue 3 https://doi.org/10.1039/C9CC07198A	journal	January 2020
Multiple-responsive supramolecular vesicle based on azobenzene–cyclodextrin host–guest interaction Wang, Jiao; Wang, Ting; Liu, Xiaohui RSC Advances, Vol. 10, Issue 32 https://doi.org/10.1039/D0RA02123G	journal	January 2020
Combining supramolecular chemistry with biology Uhlenheuer, Dana A.; Petkau, Katja; Brunsveld, Luc Chemical Society Reviews, Vol. 39, Issue 8 https://doi.org/10.1039/b820283b	journal	January 2010
Azobenzene photoswitches for biomolecules Beharry, Andrew A.; Woolley, G. Andrew Chemical Society Reviews, Vol. 40, Issue 8 https://doi.org/10.1039/c1cs15023e	journal	January 2011
Supramolecular assembling systems formed by heme–heme pocket interactions in hemoproteins Oohora, Koji; Onoda, Akira; Hayashi, Takashi Chemical Communications, Vol. 48, Issue 96 https://doi.org/10.1039/c2cc36376c	journal	January 2012
PNAS Plus: From the Cover: A gating mechanism of pentameric ligand-gated ion channels Calimet, N.; Simoes, M.; Changeux, J. -P. Proceedings of the National Academy of Sciences, Vol. 110, Issue 42 https://doi.org/10.1073/pnas.1313785110	journal	September 2013
Model2SAS: software for small-angle scattering data calculation from custom shapes Li, Mu; Yin, Panchao Journal of Applied Crystallography, Vol. 55, Issue 3 https://doi.org/10.1107/S1600576722003600	journal	May 2022
Diverse cytomotive actins and tubulins share a polymerization switch mechanism conferring robust dynamics Wagstaff, James Mark; Planelles-Herrero, Vicente José; Sharov, Grigory Science Advances, Vol. 9, Issue 13 https://doi.org/10.1126/sciadv.adf3021	journal	March 2023
A One-Domain Voltage-Gated Sodium Channel in Bacteria Catterall, William A. Science, Vol. 294, Issue 5550 https://doi.org/10.1126/science.1067417	journal	December 2001
Self-Assembly of Proteins into Designed Networks Ringler, P. Science, Vol. 302, Issue 5642 https://doi.org/10.1126/science.1088074	journal	October 2003
Allosteric Mechanisms of Signal Transduction Changeux, J. -P. Science, Vol. 308, Issue 5727 https://doi.org/10.1126/science.1108595	journal	June 2005
Host-Guest Chemistry: Complexes between organic compounds simulate the substrate selectivity of enzymes Cram, D. J.; Cram, J. M. Science, Vol. 183, Issue 4127 https://doi.org/10.1126/science.183.4127.803	journal	March 1974
Supramolecular Chemistry: Receptors, Catalysts, and Carriers Lehn, J. -M. Science, Vol. 227, Issue 4689 https://doi.org/10.1126/science.227.4689.849	journal	February 1985
Controlling signal transduction with synthetic ligands Spencer, D.; Wandless, T.; Schreiber, S. Science, Vol. 262, Issue 5136 https://doi.org/10.1126/science.7694365	journal	November 1993
Building two-dimensional materials one row at a time: Avoiding the nucleation barrier Chen, Jiajun; Zhu, Enbo; Liu, Juan Science, Vol. 362, Issue 6419 https://doi.org/10.1126/science.aau4146	journal	December 2018
Robust deep learning–based protein sequence design using ProteinMPNN Dauparas, J.; Anishchenko, I.; Bennett, N. Science, Vol. 378, Issue 6615 https://doi.org/10.1126/science.add2187	journal	October 2022
Structure, Dynamics, Assembly, and Evolution of Protein Complexes Marsh, Joseph A.; Teichmann, Sarah A. Annual Review of Biochemistry, Vol. 84, Issue 1 https://doi.org/10.1146/annurev-biochem-060614-034142	journal	June 2015
Disulfide Bonding in Protein Biophysics Fass, Deborah Annual Review of Biophysics, Vol. 41, Issue 1 https://doi.org/10.1146/annurev-biophys-050511-102321	journal	June 2012
Theoretical and Computational Protein Design Samish, Ilan; MacDermaid, Christopher M.; Perez-Aguilar, Jose Manuel Annual Review of Physical Chemistry, Vol. 62, Issue 1 https://doi.org/10.1146/annurev-physchem-032210-103509	journal	May 2011
Allosteric Models for Cooperative Polymerization of Linear Polymers Miraldi, Emily R.; Thomas, Peter J.; Romberg, Laura Biophysical Journal, Vol. 95, Issue 5 https://doi.org/10.1529/biophysj.107.126219	journal	September 2008
Principles of Crystal Nucleation and Growth De Yoreo, J. J. Reviews in Mineralogy and Geochemistry, Vol. 54, Issue 1 https://doi.org/10.2113/0540057	journal	January 2003

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