gp41: HIVs shy protein

摘要

The HIV-1 envelope spike is a putative trimer of gp120-gp41 heterodimers. ( ) Before fusion. In the native, untriggered conformation, the ectodomain (extraviral portion) of gp41 is largely cloaked by gp120 (transparent here). The structural details of this native configuration are not well elucidated. ( ) Fusion intermediate(s). Upon binding CD4 and coreceptor, gp120 undergoes conformational changes that expose gp41 and activate the fusion machinery, notably the N-HR regions and the fusion peptide (FP). gp41 is probably in a somewhat extended arrangement in which the N-HR region of three gp41 molecules form an α-helical bundle, positioning the fusion peptides for insertion into the host-cell membrane. The C-HR region of gp41 is drawn here without defined secondary structure, but some models show it in an α-helical conformation. gp41-targeting fusion inhibitors such as T20 act on the fusion-intermediate conformation(s) of gp41 to inhibit six-helix bundle formation. ( ) After fusion. Fusion seems to coincide with chain reversal, or 'jackknifing', such that the antiparallel N-HR and C-HR regions form a six-helix bundle, represented here by the structure of Weissenhorn . .