Abstract

The envelope (Env) spikes on HIV-1 and closely related SIV define the viral tropism, mediate the fusion process and are the prime target of the humoral response. Despite intensive efforts, Env has been slow to reveal its structural and functional secrets. Three gp120 subunits comprise the 'head' of Env and three gp41 subunits comprise the 'stalk' and other membrane-associated elements. The recent description of the core structure of unliganded (untriggered) gp120, compared to earlier CD4-liganded atomic structures, reveals dramatic conformational reorganization of the components and suggests a mechanism for the initiation of fusion. The structure of the key V3 loop, both in isolation and in association with the liganded core, helps define its role in fusion and as a prime target of neutralizing antibodies. Additional details are emerging regarding the structure of gp41 as it transitions from the preliganded configuration to the fusion intermediate (fusion-active or prehairpin intermediate) configuration, although much remains speculative. Recent advances in cryoelectron tomography are giving us the first glimpses of the overall three-dimensional structure of Env, which, when fitted with the available component atomic structures, provides new insights into the organization of the structural elements within the trimeric spike.