1. Crystal structure of the chemokine receptor CXCR4 in complex with a viral chemokine
- Author
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Qin, Ling, Kufareva, Irina, Holden, Lauren G, Wang, Chong, Zheng, Yi, Zhao, Chunxia, Fenalti, Gustavo, Wu, Huixian, Han, Gye Won, Cherezov, Vadim, Abagyan, Ruben, Stevens, Raymond C, and Handel, Tracy M
- Subjects
Biochemistry and Cell Biology ,Chemical Sciences ,Biological Sciences ,Emerging Infectious Diseases ,Biodefense ,Vaccine Related ,Prevention ,Infectious Diseases ,2.1 Biological and endogenous factors ,Aetiology ,1.1 Normal biological development and functioning ,Underpinning research ,Inflammatory and immune system ,Amino Acid Sequence ,Chemokine CXCL12 ,Chemokines ,Crystallography ,X-Ray ,Drug Design ,Humans ,Models ,Chemical ,Molecular Sequence Data ,Protein Binding ,Protein Interaction Domains and Motifs ,Protein Multimerization ,Receptors ,CXCR4 ,Structural Homology ,Protein ,General Science & Technology - Abstract
Chemokines and their receptors control cell migration during development, immune system responses, and in numerous diseases, including inflammation and cancer. The structural basis of receptor:chemokine recognition has been a long-standing unanswered question due to the challenges of structure determination for membrane protein complexes. Here, we report the crystal structure of the chemokine receptor CXCR4 in complex with the viral chemokine antagonist vMIP-II at 3.1 angstrom resolution. The structure revealed a 1:1 stoichiometry and a more extensive binding interface than anticipated from the paradigmatic two-site model. The structure helped rationalize a large body of mutagenesis data and together with modeling provided insights into CXCR4 interactions with its endogenous ligand CXCL12, its ability to recognize diverse ligands, and the specificity of CC and CXC receptors for their respective chemokines.
- Published
- 2015