Molecular modeling on human CCR5 receptors and complex with CD4 antigens and HIV-1 envelope glycoprotein gp120.
OBJECTIVE
To investigate the interaction between human CCR5 receptors (CCR5) and HIV-1 envelope glycoprotein gp120 (HIV-1 gp120) and HIV-1 receptor CD4 antigens (CD4).


METHODS
The structurally conserved regions (SCR) of human CCR5 was built by the SYBYL/Biopolymer module using the corresponding transmembrane (TM) domain of bacteriorhodopsin (bR) as the template. The coordinates for amino-terminal residue sequence, and carboxyl-terminal residue sequence, extracellular and cytoplasmic loops were generated using LOOP SEARCH algorithm. Subsequently the structural model was merged into the complex with HIV-1 gp120 and CD4.


RESULTS
Human CCR5 interacted with both an HIV-1 gp120 and CD4. The N-terminal residues (especially Met1 and Gln4) of human CCR5 contacted with CD4 residues, mainly with one span (56-59) of CD4 in electrostatic interaction and hydrogen-bonds. The binding sites of human CCR5 were buried in a hydrophobic center surrounded by a highly basic periphery. On the other hand, direct interatomic contacts were made between 7 CCR5 residues and 6 gp120 amino-acid residues, which included van der Waals contacts, hydrophobic interaction, and hydrogen bonds.


CONCLUSIONS
The interaction model should be helpful for rational design of novel anti-HIV drugs.
Yang
J
J
Laboratory of Cellular and Molecular Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
Liu
C Q
CQ
D015704:CD4 Antigens / Q000737:chemistry*; D004347:Drug Interactions; D015699:HIV Envelope Protein gp120 / Q000737:chemistry*; D015497:HIV-1 / Q000737:chemistry*; D008958:Models, Molecular; D019713:Receptors, CCR5 / Q000737:chemistry*
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D019713:Receptors, CCR5