HIV-1 capsid plays multiple key roles in viral replication, and inhibition of capsid assembly is an attractive target for therapeutic intervention. Here, we report the atomic-resolution structure of capsid protein (CA) tubes, determined by magic-angle spinning NMR and data-guided molecular dynamics simulations. Functionally important regions, including the NTD β-hairpin, the cyclophilin A-binding loop, residues in the hexamer central pore, and the NTD-CTD linker region, are well defined. The structure of individual CA chains, their arrangement in the pseudo-hexameric units of the tube and the inter-hexamer interfaces are consistent with those in intact capsids and substantially different from the organization in crystal structures, which feature flat hexamers. The inherent curvature in the CA tubes is controlled by conformational variability of residues in the linker region and of dimer and trimer interfaces. The present structure reveals atomic-level detail in capsid architecture and provides important guidance for the design of novel capsid inhibitors.

HIV-1 衣壳在病毒复制中发挥多种关键作用，抑制衣壳组装是治疗干预的一个有吸引力的目标。在这里，我们报告了衣壳蛋白 (CA) 管的原子分辨率结构，由魔角旋转 NMR 和数据引导的分子动力学模拟确定。功能上重要的区域，包括 NTD β-发夹、亲环蛋白 A 结合环、六聚体中心孔中的残基和 NTD-CTD 接头区域，均已明确定义。单个 CA 链的结构、它们在管的假六聚体单元中的排列和六聚体间界面与完整衣壳中的一致，而与晶体结构中的组织有很大不同，后者具有扁平的六聚体。CA 管的固有曲率受连接区残基以及二聚体和三聚体界面的构象变异性控制。目前的结构揭示了衣壳结构中的原子级细节，并为新型衣壳抑制剂的设计提供了重要指导。