Alternative conformations of HIV-1V3 loops mimic β hairpins in chemokines, suggesting a mechanism for coreceptor selectivity
Alternative conformations of HIV-1V3 loops mimic β hairpins in chemokines, suggesting a mechanism for coreceptor selectivity
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DOI：
10.1016/s0969-2126(03)00011-x
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发表时间：
2003-02-01
期刊：
影响因子：
5.7
通讯作者：
Anglister, J
中科院分区：
文献类型：
--
作者：
Sharon, M;Kessler, N;Anglister, J
HIV-1包膜糖蛋白gp120的V3环参与与CCR5和CXCR4辅助受体的结合。用核磁共振仪分析了HIV-1(MN)V3多肽与人中和抗体447-52d Fv结合的结构，发现其为β-发夹结构。V3(MN)的这种结构被发现与CD8和CCR5配体MIP-1α、MIP-1β和RANTES中的β发夹具有构象和序列相似性，而不同于V3(IIIB)多肽与菌株特异性小鼠抗gp120(IIIB)抗体0.5beta结合的β发夹。与结合的V3(MN)肽的结构相反，V3(IIIB)肽类似于CXCR4配体SDF-1的β发夹。这些数据表明，447-52d结合的V3(MN)和0.5beta结合的V3(IIIB)结构分别代表了负责与CCR5和CXCR4选择性相互作用的替代V3构象。
The V3 loop of the HIV-1 envelope glycoprotein gp120 is involved in binding to the CCR5 and CXCR4 coreceptors. The structure of an HIV-1(MN) V3 peptide bound to the Fv of the broadly neutralizing human monoclonal antibody 447-52D was solved by NMR and found to be a beta hairpin. This structure of V3(MN) was found to have conformation and sequence similarities to beta hairpins in CD8 and CCR5 ligands MIP-1alpha, MIP-1beta, and RANTES and differed from the beta hairpin of a V3(IIIB) peptide bound to the strain-specific murine anti-gp120(IIIB) antibody 0.5beta. In contrast to the structure of the bound V3(MN) peptide, the V3(IIIB) peptide resembles a beta hairpin in SDF-1, a CXCR4 ligand. These data suggest that the 447-52D-bound V3(MN) and the 0.5beta-bound V3(IIIB) structures represent alternative V3 conformations responsible for selective interactions with CCR5 and CXCR4, respectively.