The mature retrovirus capsid consists of a variably curved lattice of capsid protein (CA) hexamers and pentamers. High-resolution structures of the curved assembly, or in complex with host factors, have not been available. By devising cryo-EM methodologies for exceedingly flexible and pleomorphic assemblies, we have determined cryo-EM structures of apo-CA hexamers and in complex with cyclophilin A (CypA) at near-atomic resolutions. The CA hexamers are intrinsically curved, flexible and asymmetric, revealing the capsomere and not the previously touted dimer or trimer interfaces as the key contributor to capsid curvature. CypA recognizes specific geometries of the curved lattice, simultaneously interacting with three CA protomers from adjacent hexamers via two noncanonical interfaces, thus stabilizing the capsid. By determining multiple structures from various helical symmetries, we further revealed the essential plasticity of the CA molecule, which allows formation of continuously curved conical capsids and the mechanism of capsid pattern sensing by CypA.

成熟的逆转录病毒衣壳由衣壳蛋白 (CA) 六聚体和五聚体的可变弯曲晶格组成。弯曲组件的高分辨率结构，或与宿主因素复杂的结构，尚未获得。通过为极其灵活和多形的组件设计低温-EM 方法，我们已经确定了 apo-CA 六聚体的低温-EM 结构，并在近原子分辨率下与亲环蛋白 A (CypA) 复合。CA 六聚体本质上是弯曲的、灵活的和不对称的，揭示了衣壳而不是以前吹捧的二聚体或三聚体界面作为衣壳曲率的关键因素。CypA 识别弯曲晶格的特定几何形状，同时通过两个非规范界面与来自相邻六聚体的三个 CA 原体相互作用，从而稳定衣壳。