Structural basis of ligand interaction with atypical chemokine receptor 3

Gustavsson, Martin; Wang, Liwen; van Gils, Noortje; Stephens, Bryan S.; Zhang, Penglie; Schall, Thomas J.; Yang, Sichun; Abagyan, Ruben; Chance, Mark R.; Kufareva, Irina; Handel, Tracy M.

doi:10.1038/ncomms14135

Title: Structural basis of ligand interaction with atypical chemokine receptor 3

Journal Article · Wed Jan 18 00:00:00 EST 2017 · Nature Communications

DOI:https://doi.org/10.1038/ncomms14135· OSTI ID:1409609

Gustavsson, Martin; Wang, Liwen; van Gils, Noortje; Stephens, Bryan S.; Zhang, Penglie; Schall, Thomas J.;

; Abagyan, Ruben; Chance, Mark R.;

; Handel, Tracy M.

Chemokines drive cell migration through their interactions with seven-transmembrane (7TM) chemokine receptors on cell surfaces. The atypical chemokine receptor 3 (ACKR3) binds chemokines CXCL11 and CXCL12 and signals exclusively through β-arrestin-mediated pathways, without activating canonical G-protein signalling. This receptor is upregulated in numerous cancers making it a potential drug target. Here we collected over 100 distinct structural probes from radiolytic footprinting, disulfide trapping, and mutagenesis to map the structures of ACKR3:CXCL12 and ACKR3:small-molecule complexes, including dynamic regions that proved unresolvable by X-ray crystallography in homologous receptors. The data are integrated with molecular modelling to produce complete and cohesive experimentally driven models that confirm and expand on the existing knowledge of the architecture of receptor:chemokine and receptor:small-molecule complexes. Additionally, we detected and characterized ligand-induced conformational changes in the transmembrane and intracellular regions of ACKR3 that elucidate fundamental structural elements of agonism in this atypical receptor.

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:: 1409609

Report Number(s):: BNL-114661-2017-JA¿¿¿

Journal Information:: Nature Communications, Vol. 8; ISSN 2041-1723

Publisher:: Nature Publishing Group

Country of Publication:: United States

Language:: English

References (40)

Biased Probability Monte Carlo Conformational Searches and Electrostatic Calculations for Peptides and Proteins Abagyan, Ruben; Totrov, Maxim Journal of Molecular Biology, Vol. 235, Issue 3 https://doi.org/10.1006/jmbi.1994.1052	journal	January 1994
Crystal structure of the chemokine receptor CXCR4 in complex with a viral chemokine Qin, L.; Kufareva, I.; Holden, L. G. Science, Vol. 347, Issue 6226 https://doi.org/10.1126/science.1261064	journal	January 2015
Conformational Dynamics of Activation for the Pentameric Complex of Dimeric G Protein-Coupled Receptor and Heterotrimeric G Protein Orban, Tivadar; Jastrzebska, Beata; Gupta, Sayan Structure, Vol. 20, Issue 5 https://doi.org/10.1016/j.str.2012.03.017	journal	May 2012
Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser Kang, Yanyong; Zhou, X. Edward; Gao, Xiang Nature, Vol. 523, Issue 7562 https://doi.org/10.1038/nature14656	journal	July 2015
Conformational states of the full-length glucagon receptor Yang, Linlin; Yang, Dehua; de Graaf, Chris Nature Communications, Vol. 6, Issue 1 https://doi.org/10.1038/ncomms8859	journal	July 2015
The Beamline X28C of the Center for Synchrotron Biosciences: a National Resource for Biomolecular Structure and Dynamics Experiments Using Synchrotron Footprinting Gupta, Sayan; Sullivan, Michael; Toomey, John Journal of Synchrotron Radiation, Vol. 14, Issue 3 https://doi.org/10.1107/S0909049507013118	journal	April 2007
Structure-Based Identification of Novel Ligands Targeting Multiple Sites within a Chemokine–G-Protein-Coupled-Receptor Interface Smith, Emmanuel W.; Nevins, Amanda M.; Qiao, Zhen Journal of Medicinal Chemistry, Vol. 59, Issue 9 https://doi.org/10.1021/acs.jmedchem.5b02042	journal	April 2016
-arrestin- but not G protein-mediated signaling by the "decoy" receptor CXCR7 Rajagopal, S.; Kim, J.; Ahn, S. Proceedings of the National Academy of Sciences, Vol. 107, Issue 2 https://doi.org/10.1073/pnas.0912852107	journal	December 2009
Activation of G-protein-coupled receptors correlates with the formation of a continuous internal water pathway Yuan, Shuguang; Filipek, Slawomir; Palczewski, Krzysztof Nature Communications, Vol. 5, Issue 1 https://doi.org/10.1038/ncomms5733	journal	September 2014
The significance of cancer cell expression of the chemokine receptor CXCR4 Balkwill, Fran Seminars in Cancer Biology, Vol. 14, Issue 3 https://doi.org/10.1016/j.semcancer.2003.10.003	journal	June 2004
Biased agonism: An emerging paradigm in GPCR drug discovery Rankovic, Zoran; Brust, Tarsis F.; Bohn, Laura M. Bioorganic & Medicinal Chemistry Letters, Vol. 26, Issue 2 https://doi.org/10.1016/j.bmcl.2015.12.024	journal	January 2016
Sulfopeptide Probes of the CXCR4/CXCL12 Interface Reveal Oligomer-Specific Contacts and Chemokine Allostery Ziarek, Joshua J.; Getschman, Anthony E.; Butler, Stephen J. ACS Chemical Biology, Vol. 8, Issue 9 https://doi.org/10.1021/cb400274z	journal	June 2013
A mass accuracy sensitive probability based scoring algorithm for database searching of tandem mass spectrometry data Xu, Hua; Freitas, Michael A. BMC Bioinformatics, Vol. 8, Issue 1 https://doi.org/10.1186/1471-2105-8-133	journal	April 2007
Radiolytic Modification and Reactivity of Amino Acid Residues Serving as Structural Probes for Protein Footprinting Xu, Guozhong; Chance, Mark R. Analytical Chemistry, Vol. 77, Issue 14 https://doi.org/10.1021/ac050299+	journal	June 2005
Microscale Fluorescent Thermal Stability Assay for Membrane Proteins Alexandrov, Alexander I.; Mileni, Mauro; Chien, Ellen Y. T. Structure, Vol. 16, Issue 3 https://doi.org/10.1016/j.str.2008.02.004	journal	March 2008
Signal transmission through the CXC chemokine receptor 4 (CXCR4) transmembrane helices Wescott, Melanie P.; Kufareva, Irina; Paes, Cheryl Proceedings of the National Academy of Sciences, Vol. 113, Issue 35 https://doi.org/10.1073/pnas.1601278113	journal	August 2016
Biased Signaling Pathways in 2-Adrenergic Receptor Characterized by 19F-NMR Liu, J. J.; Horst, R.; Katritch, V. Science, Vol. 335, Issue 6072 https://doi.org/10.1126/science.1215802	journal	January 2012
Prediction of the binding energy for small molecules, peptides and proteins Schapira, Matthieu; Totrov, Maxim; Abagyan, Ruben Journal of Molecular Recognition, Vol. 12, Issue 3 https://doi.org/10.1002/(SICI)1099-1352(199905/06)12:3<177::AID-JMR451>3.0.CO;2-Z	journal	May 1999
Methodological advances: the unsung heroes of the GPCR structural revolution Ghosh, Eshan; Kumari, Punita; Jaiman, Deepika Nature Reviews Molecular Cell Biology, Vol. 16, Issue 2 https://doi.org/10.1038/nrm3933	journal	January 2015
Structure of the CCR5 Chemokine Receptor-HIV Entry Inhibitor Maraviroc Complex Tan, Q.; Zhu, Y.; Li, J. Science, Vol. 341, Issue 6152 https://doi.org/10.1126/science.1241475	journal	September 2013
Quantitative Mapping of Protein Structure by Hydroxyl Radical Footprinting-Mediated Structural Mass Spectrometry: A Protection Factor Analysis Huang, Wei; Ravikumar, Krishnakumar M.; Chance, Mark R. Biophysical Journal, Vol. 108, Issue 1 https://doi.org/10.1016/j.bpj.2014.11.013	journal	January 2015
Stoichiometry and geometry of the CXC chemokine receptor 4 complex with CXC ligand 12: Molecular modeling and experimental validation Kufareva, Irina; Stephens, Bryan S.; Holden, Lauren G. Proceedings of the National Academy of Sciences, Vol. 111, Issue 50 https://doi.org/10.1073/pnas.1417037111	journal	December 2014
Allosteric sodium in class A GPCR signaling Katritch, Vsevolod; Fenalti, Gustavo; Abola, Enrique E. Trends in Biochemical Sciences, Vol. 39, Issue 5 https://doi.org/10.1016/j.tibs.2014.03.002	journal	May 2014
Crystal Structure of Rhodopsin: A G Protein-Coupled Receptor Palczewski, K. Science, Vol. 289, Issue 5480 https://doi.org/10.1126/science.289.5480.739	journal	August 2000
Structures of the CXCR4 Chemokine GPCR with Small-Molecule and Cyclic Peptide Antagonists Wu, B.; Chien, E. Y. T.; Mol, C. D. Science, Vol. 330, Issue 6007 https://doi.org/10.1126/science.1194396	journal	October 2010
Crystal structure of the β2 adrenergic receptor–Gs protein complex Rasmussen, Søren G. F.; DeVree, Brian T.; Zou, Yaozhong Nature, Vol. 477, Issue 7366 https://doi.org/10.1038/nature10361	journal	July 2011
Conserved waters mediate structural and functional activation of family A (rhodopsin-like) G protein-coupled receptors Angel, T. E.; Chance, M. R.; Palczewski, K. Proceedings of the National Academy of Sciences, Vol. 106, Issue 21 https://doi.org/10.1073/pnas.0903545106	journal	May 2009
Effective Application of Bicelles for Conformational Analysis of G Protein-Coupled Receptors by Hydrogen/Deuterium Exchange Mass Spectrometry Duc, Nguyen Minh; Du, Yang; Thorsen, Thor S. Journal of The American Society for Mass Spectrometry, Vol. 26, Issue 5 https://doi.org/10.1007/s13361-015-1083-4	journal	March 2015
Quantitative Protein Topography Analysis and High-Resolution Structure Prediction Using Hydroxyl Radical Labeling and Tandem-Ion Mass Spectrometry (MS) Kaur, Parminder; Kiselar, Janna; Yang, Sichun Molecular & Cellular Proteomics, Vol. 14, Issue 4 https://doi.org/10.1074/mcp.O114.044362	journal	February 2015
Structural Mass Spectrometry of Proteins Using Hydroxyl Radical Based Protein Footprinting Wang, Liwen; Chance, Mark R. Analytical Chemistry, Vol. 83, Issue 19 https://doi.org/10.1021/ac200567u	journal	October 2011
Crystal structure of chemically synthesized [N33A] stromal cell-derived factor 1 , a potent ligand for the HIV-1 "fusin" coreceptor Dealwis, C.; Fernandez, E. J.; Thompson, D. A. Proceedings of the National Academy of Sciences, Vol. 95, Issue 12 https://doi.org/10.1073/pnas.95.12.6941	journal	June 1998
Molecular control of δ-opioid receptor signalling Fenalti, Gustavo; Giguere, Patrick M.; Katritch, Vsevolod Nature, Vol. 506, Issue 7487 https://doi.org/10.1038/nature12944	journal	January 2014
Structural Basis of CXCR4 Sulfotyrosine Recognition by the Chemokine SDF-1/CXCL12 Veldkamp, C. T.; Seibert, C.; Peterson, F. C. Science Signaling, Vol. 1, Issue 37 https://doi.org/10.1126/scisignal.1160755	journal	September 2008
Molecular signatures of G-protein-coupled receptors Venkatakrishnan, A. J.; Deupi, Xavier; Lebon, Guillaume Nature, Vol. 494, Issue 7436 https://doi.org/10.1038/nature11896	journal	February 2013
Structural insights into µ-opioid receptor activation Huang, Weijiao; Manglik, Aashish; Venkatakrishnan, A. J. Nature, Vol. 524, Issue 7565 https://doi.org/10.1038/nature14886	journal	August 2015
Structural basis for chemokine recognition and activation of a viral G protein-coupled receptor Burg, J. S.; Ingram, J. R.; Venkatakrishnan, A. J. Science, Vol. 347, Issue 6226 https://doi.org/10.1126/science.aaa5026	journal	March 2015
Structural waters define a functional channel mediating activation of the GPCR, rhodopsin Angel, T. E.; Gupta, S.; Jastrzebska, B. Proceedings of the National Academy of Sciences, Vol. 106, Issue 34 https://doi.org/10.1073/pnas.0901074106	journal	August 2009
Identification and Characterization of Disulfide Bonds in Proteins and Peptides from Tandem MS Data by Use of the MassMatrix MS/MS Search Engine Xu, Hua; Zhang, Liwen; Freitas, Michael A. Journal of Proteome Research, Vol. 7, Issue 1 https://doi.org/10.1021/pr070363z	journal	January 2008
A Hybrid Structural Approach to Analyze Ligand Binding by the Serotonin Type 4 Receptor (5-HT4) Padayatti, Pius S.; Wang, Liwen; Gupta, Sayan Molecular & Cellular Proteomics, Vol. 12, Issue 5 https://doi.org/10.1074/mcp.M112.025536	journal	February 2013
Chemokines and Chemokine Receptors: Positioning Cells for Host Defense and Immunity Griffith, Jason W.; Sokol, Caroline L.; Luster, Andrew D. Annual Review of Immunology, Vol. 32, Issue 1 https://doi.org/10.1146/annurev-immunol-032713-120145	journal	March 2014

Similar Records

Heterologous Quaternary Structure of CXCL12 and its Relationship to the CC Chemokine Family

Journal Article · Fri Jan 01 00:00:00 EST 2010 · Proteins: Structure, Functions, and Bioinformatics · OSTI ID:1409609

Murphy, J; Yuan, H; Kong, Y; +2 more

VPS26 Moonlights as an Arrestin-like Adapter for a 7-transmembrane RGS 2 protein in Arabidopsis thaliana

Technical Report · Tue Mar 07 00:00:00 EST 2023 · OSTI ID:1409609

Jones, Alan M.

Solution structure of the complex between poxvirus-encoded CC chemokine inhibitor vCCI and human MIP-1β

Journal Article · Tue Sep 19 00:00:00 EDT 2006 · Proceedings of the National Academy of Sciences of the United States of America, 103(38):13985-13990 · OSTI ID:1409609

Zhang, Li; DeRider, Michele; McCornack, Milissa A; +5 more

Related Subjects

60 APPLIED LIFE SCIENCES
59 BASIC BIOLOGICAL SCIENCES

Title: Structural basis of ligand interaction with atypical chemokine receptor 3

Citation Formats

References (40)

Similar Records

Related Subjects