3OE8

Crystal structure of the CXCR4 chemokine receptor in complex with a small molecule antagonist IT1t in P1 spacegroup

Summary for 3OE8

• Entry DOI: 10.2210/pdb3oe8/pdb
• Related: 3ODU 3OE0 3OE6 3OE9
• Descriptor: C-X-C chemokine receptor type 4, Lysozyme Chimera, (6,6-dimethyl-5,6-dihydroimidazo[2,1-b][1,3]thiazol-3-yl)methyl N,N'-dicyclohexylimidothiocarbamate (2 entities in total)
• Functional Keywords: structural genomics, psi-2, protein structure initiative, accelerated technologies center for gene to 3d structure, atcg3d, 7tm, g protein-coupled receptor, gpcr, signal transduction, hydrolase, cancer, hiv-1 co-receptor, chemotaxis, chemokine, cxcl12, sdf1, isothiourea, chimera, t4l fusion, membrane protein, transmembrane, singnaling protein, psi-biology, gpcr network, signaling protein
• Biological source: Homo Sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 172108.36

Authors

Wu, B.,Mol, C.D.,Han, G.W.,Katritch, V.,Chien, E.Y.T.,Liu, W.,Cherezov, V.,Stevens, R.C.,Accelerated Technologies Center for Gene to 3D Structure (ATCG3D),GPCR Network (GPCR) (deposition date: 2010-08-12, release date: 2010-10-27, Last modification date: 2024-10-16)

Primary citation

Wu, B.,Chien, E.Y.,Mol, C.D.,Fenalti, G.,Liu, W.,Katritch, V.,Abagyan, R.,Brooun, A.,Wells, P.,Bi, F.C.,Hamel, D.J.,Kuhn, P.,Handel, T.M.,Cherezov, V.,Stevens, R.C.
Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists.
Science, 330:1066-1071, 2010

PubMed 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.

PubMed: 20929726
DOI: 10.1126/science.1194396

Experimental method

X-RAY DIFFRACTION (3.1 Å)