Subunit organization of the membrane-bound HIV-1 envelope glycoprotein trimer

Y Mao, L Wang, C Gu, A Herschhorn… - Nature structural & …, 2012 - nature.com
Y Mao, L Wang, C Gu, A Herschhorn, SH Xiang, H Haim, X Yang, J Sodroski
Nature structural & molecular biology, 2012nature.com
The trimeric human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env)
spike is a molecular machine that mediates virus entry into host cells and is the sole target
for virus-neutralizing antibodies. The mature Env spike results from cleavage of a trimeric
glycoprotein precursor, gp160, into three gp120 and three gp41 subunits. Here, we describe
an~ 11-Å cryo-EM structure of the trimeric HIV-1 Env precursor in its unliganded state. The
three gp120 and three gp41 subunits form a cage-like structure with an interior void …
Abstract
The trimeric human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) spike is a molecular machine that mediates virus entry into host cells and is the sole target for virus-neutralizing antibodies. The mature Env spike results from cleavage of a trimeric glycoprotein precursor, gp160, into three gp120 and three gp41 subunits. Here, we describe an ~11-Å cryo-EM structure of the trimeric HIV-1 Env precursor in its unliganded state. The three gp120 and three gp41 subunits form a cage-like structure with an interior void surrounding the trimer axis. Interprotomer contacts are limited to the gp41 transmembrane region, the torus-like gp41 ectodomain and a trimer-association domain of gp120 composed of the V1, V2 and V3 variable regions. The cage-like architecture, which is unique among characterized viral envelope proteins, restricts antibody access, reflecting requirements imposed by HIV-1 persistence in the host.
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