Structures of the CXCR4 Chemokine GPCR with Small-Molecule and Cyclic Peptide Antagonists
Wu, Beili; Chien, Ellen Y. T.; Mol, Clifford D.; Fenalti, Gustavo; Liu, Wei; Katritch, Vsevolod; Abagyan, Ruben; Brooun, Alexei; Wells, Peter; Bi, F. Christopher; Hamel, Damon J.; Kuhn, Peter; Handel, Tracy M.; Cherezov, Vadim; Stevens, Raymond C.
2010
Source PublicationSCIENCE
ISSN0036-8075
EISSN1095-9203
Volume330Issue:6007Pages:166-171
Status已发表
DOI10.1126/science.1194396
Abstract

Chemokine receptors are critical regulators of cell migration in the context of immune surveillance, inflammation, and development. The G protein-coupled chemokine receptor CXCR4 is specifically implicated in cancer metastasis and HIV-1 infection. Here we report five independent crystal structures of CXCR4 bound to an antagonist small molecule IT1t and a cyclic peptide CVX15 at 2.5 to 3.2 angstrom resolution. All structures reveal a consistent homodimer with an interface including helices V and VI that may be involved in regulating signaling. The location and shape of the ligand-binding sites differ from other G protein-coupled receptors and are closer to the extracellular surface. These structures provide new clues about the interactions between CXCR4 and its natural ligand CXCL12, and with the HIV-1 glycoprotein gp120.

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Indexed BySCI
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000284374700033
PublisherAMER ASSOC ADVANCEMENT SCIENCE
WOS KeywordANTI-HIV ACTIVITY ; CRYSTAL-STRUCTURE ; RECEPTOR DIMERIZATION ; LIGAND ; GP120 ; REVEALS ; IDENTIFICATION ; MIGRATION ; RESIDUES ; CELLS
Original Document TypeArticle
Citation statistics
Cited Times:1332[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttps://kms.shanghaitech.edu.cn/handle/2MSLDSTB/119774
Collection个人在本单位外知识产出
Corresponding AuthorStevens, Raymond C.
Affiliation1.Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA
2.Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA
3.Univ Calif San Diego, San Diego Supercomp Ctr, La Jolla, CA 92093 USA
4.Pfizer Worldwide Res & Dev, San Diego, CA 92121 USA
Recommended Citation
GB/T 7714
Wu, Beili,Chien, Ellen Y. T.,Mol, Clifford D.,et al. Structures of the CXCR4 Chemokine GPCR with Small-Molecule and Cyclic Peptide Antagonists[J]. SCIENCE,2010,330(6007):166-171.
APA Wu, Beili.,Chien, Ellen Y. T..,Mol, Clifford D..,Fenalti, Gustavo.,Liu, Wei.,...&Stevens, Raymond C..(2010).Structures of the CXCR4 Chemokine GPCR with Small-Molecule and Cyclic Peptide Antagonists.SCIENCE,330(6007),166-171.
MLA Wu, Beili,et al."Structures of the CXCR4 Chemokine GPCR with Small-Molecule and Cyclic Peptide Antagonists".SCIENCE 330.6007(2010):166-171.
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