title: Theoretical studies on the interactions and interferences of HIV-1 glycoprotein gp120 and its coreceptor CCR5.
abstract: The interaction between the HIV gp120 protein and coreceptor CCR5 or CXCR4 of the host cell is critical in mediating the HIV entry process. A model for the CCR5-gp120 complex has been developed. In the model, the N-terminus of CCR5 binds to three discontinuous domains of gp120, including the fourth conserved (C4) region, β19/β20 connecting loop, and V3 loop. The second extra-cellular loop (ECL2) of CCR5 also interacts with the crown part of the gp120 V3 loop. The bindings of the three CCR5 antagonists, maraviroc, aplaviroc, and vicriviroc, to the trans-membrane domain of CCR5 have been modeled. The bindings are found to affect the conformation of the ECL2 domain, which in turn drives the N-terminus of CCR5 to an altered state. Aplaviroc is more hydrophilic than maraviroc and vicriviroc, and its binding is more interfered by solvent, resulting in a quite different effect to the structure of CCR5 compared with those of the other two molecules. The above results are in accord with experimental observations and provide a structural basis for further design of CCR5 antagonists.
authors.affiliation: School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, China.
authors.forename: Lin-tai
authors.initials: LT
authors.lastname: Da
authors.forename: Yun-Dong
authors.initials: YD
authors.lastname: Wu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D065100:CCR5 Receptor Antagonists; D002417:Cattle; D054405:Chemokine CCL3 / Q000378:metabolism; D054407:Chemokine CCL4 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000378:metabolism*; D015497:HIV-1; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary / Q000187:drug effects; D019713:Receptors, CCR5 / Q000737:chemistry / Q000378:metabolism*
chemical_list: D065100:CCR5 Receptor Antagonists; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D015699:HIV Envelope Protein gp120; D019713:Receptors, CCR5; C514793:gp120 protein, Human immunodeficiency virus 1