Structural basis for chemokine recognition and activation of a viral G protein-coupled receptor

被引：229

作者：

Burg, John S. ^{[1
,2
,3
]}

Ingram, Jessica R. ^{[4
]}

Venkatakrishnan, A. J. ^{[3
,5
,6
]}

Jude, Kevin M. ^{[1
,2
,3
]}

Dukkipati, Abhiram ^{[1
,2
,3
]}

Feinberg, Evan N. ^{[3
,5
,6
]}

Angelini, Alessandro ^{[7
]}

Waghray, Deepa ^{[1
,2
,3
]}

Dror, Ron O. ^{[3
,5
,6
]}

Ploegh, Hidde L. ^{[4
]}

Garcia, K. Christopher ^{[1
,2
,3
]}

机构：

[1] Stanford Univ, Howard Hughes Med Inst, Sch Med, Stanford, CA 94305 USA

[2] Stanford Univ, Dept Biol Struct, Sch Med, Stanford, CA 94305 USA

[3] Stanford Univ, Dept Mol & Cellular Physiol, Sch Med, Stanford, CA 94305 USA

[4] Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA

[5] Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA

[6] Stanford Univ, Inst Computat & Math Engn, Stanford, CA 94305 USA

[7] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA

来源：

SCIENCE | 2015年 / 347卷 / 6226期

基金：

瑞士国家科学基金会;

关键词：

SULFOTYROSINE RECOGNITION; SIGNALING NETWORKS; CRYSTAL-STRUCTURE; IDENTIFICATION; COMPLEX; BINDING; DOMAIN;

D O I：

10.1126/science.aaa5026

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Chemokines are small proteins that function as immune modulators through activation of chemokine G protein-coupled receptors (GPCRs). Several viruses also encode chemokines and chemokine receptors to subvert the host immune response. How protein ligands activate GPCRs remains unknown. We report the crystal structure at 2.9 angstrom resolution of the human cytomegalovirus GPCR US28 in complex with the chemokine domain of human CX3CL1 (fractalkine). The globular body of CX3CL1 is perched on top of the US28 extracellular vestibule, whereas its amino terminus projects into the central core of US28. The transmembrane helices of US28 adopt an active-state-like conformation. Atomic-level simulations suggest that the agonist-independent activity of US28 may be due to an amino acid network evolved in the viral GPCR to destabilize the receptor's inactive state.

引用

页码：1113 / 1117

页数：5

共 30 条

[1]

Ballesteros J. A., 1995, METH NEUROSCI, V25, P366, DOI [10.1016/S1043-9471(05)80049-7, DOI 10.1016/S1043-9471(05)80049-7]

[2] A new class of membrane-bound chemokine with a CX(3)C motif [J].

Bazan, JF ;

Bacon, KB ;

Hardiman, G ;

Wang, W ;

Soo, K ;

Rossi, D ;

Greaves, DR ;

Zlotnik, A ;

Schall, TJ .

NATURE, 1997, 385 (6617) :640-644

[3] Identification of residues of CXCR4 critical for human immunodeficiency virus coreceptor and chemokine receptor activities [J].

Brelot, A ;

Heveker, N ;

Montes, M ;

Alizon, M .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (31) :23736-23744

[4] The second intracellular loop of the m5 muscarinic receptor is the switch which enables G-protein coupling [J].

Burstein, ES ;

Spalding, TA ;

Brann, MR .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (38) :24322-24327

[5] Identification of the first nonpeptidergic inverse agonist for a constitutively active viral-encoded G protein-coupled receptor [J].

Casarosa, P ;

Menge, WM ;

Minisini, R ;

Otto, C ;

van Heteren, J ;

Jongejan, A ;

Timmerman, H ;

Moepps, B ;

Kirchhoff, F ;

Mertens, T ;

Smit, MJ ;

Leurs, R .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (07) :5172-5178

[6] Mechanisms of disease - The many roles of chemokines and chemokine receptors in inflammation [J].

Charo, IF ;

Ransohoff, RM .

NEW ENGLAND JOURNAL OF MEDICINE, 2006, 354 (06) :610-621

[7] HUMAN CYTOMEGALOVIRUS ENCODES 3 G-PROTEIN-COUPLED RECEPTOR HOMOLOGS [J].

CHEE, MS ;

SATCHWELL, SC ;

PREDDIE, E ;

WESTON, KM ;

BARRELL, BG .

NATURE, 1990, 344 (6268) :774-777

[8] Stabilized G protein binding site in the structure of constitutively active metarhodopsin-II [J].

Deupi, Xavier ;

Edwards, Patricia ;

Singhal, Ankita ;

Nickle, Benjamin ;

Oprian, Daniel ;

Schertler, Gebhard ;

Standfuss, Joerg .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (01) :119-124

[9] Activation mechanism of the β2-adrenergic receptor [J].

Dror, Ron O. ;

Arlow, Daniel H. ;

Maragakis, Paul ;

Mildorf, Thomas J. ;

Pan, Albert C. ;

Xu, Huafeng ;

Borhani, David W. ;

Shaw, David E. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (46) :18684-18689

[10] Structural basis for modulation of a G-protein-coupled receptor by allosteric drugs [J].

Dror, Ron O. ;

Green, Hillary F. ;

Valant, Celine ;

Borhani, David W. ;

Valcourt, James R. ;

Pan, Albert C. ;

Arlow, Daniel H. ;

Canals, Meritxell ;

Lane, J. Robert ;

Rahmani, Raphael ;

Baell, Jonathan B. ;

Sexton, Patrick M. ;

Christopoulos, Arthur ;

Shaw, David E. .

NATURE, 2013, 503 (7475) :295-+

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