Biophysical methods and x-ray crystallography have revealed that class A G protein–coupled receptors (GPCRs) can form homodimers. We combined computational approaches with receptor cross-linking, energy transfer, and a newly developed functional export assay to characterize the residues involved in the dimerization interfaces of the chemokine receptor CCR5, the major co-receptor for HIV-1 entry into cells. We provide evidence of three distinct CCR5 dimeric organizations, involving residues of transmembrane helix 5. Two dimeric states corresponded to unliganded receptors, whereas the binding of the inverse agonist maraviroc stabilized a third state. We found that CCR5 dimerization was required for targeting the receptor to the plasma membrane. These data suggest that dimerization contributes to the conformational diversity of inactive class A GPCRs and may provide new opportunities to investigate the cellular entry of HIV-1 and mechanisms for its inhibition.

生物物理方法和X射线晶体学分析表明，AG类蛋白偶联受体（GPCR）可以形成同型二聚体。我们将计算方法与受体交联，能量转移和新开发的功能输出分析相结合，以表征趋化因子受体CCR5（HIV-1进入细胞的主要辅助受体）的二聚化界面所涉及的残基。我们提供了三个不同的CCR5二聚体组织的证据，涉及跨膜螺旋5的残基。两个二聚体状态对应于未配体受体，而反向激动剂maraviroc的结合稳定了第三状态。我们发现，CCR5二聚化是将受体靶向质膜所必需的。