TY - JOUR
T1 - CD4-induced activation in a soluble HIV-1 Env trimer
AU - Guttman, Miklos
AU - Garcia, Natalie K.
AU - Cupo, Albert
AU - Matsui, Tsutomu
AU - Julien, Jean-Philippe
AU - Sanders, Rogier W.
AU - Wilson, Ian A.
AU - Moore, John P.
AU - Lee, Kelly K.
PY - 2014
Y1 - 2014
N2 - The HIV envelope glycoprotein (Env) trimer undergoes receptor-induced conformational changes that drive fusion of the viral and cellular membranes. Env conformational changes have been observed using low-resolution electron microscopy, but only large-scale rearrangements have been visible. Here, we use hydrogen-deuterium exchange and oxidative labeling to gain a more precise understanding of the unliganded and CD4-bound forms of soluble Env trimers (SOSIP.664), including their glycan composition. CD4 activation induces the reorganization of bridging sheet elements, V1/V2 and V3, much of the gp120 inner domain, and the gp41 fusion subunit. Two CD4 binding site-targeted inhibitors have substantially different effects: NBD-556 partially mimics CD4-induced destabilization of the V1/V2 and V3 crown, whereas BMS-806 only affects regions around the gp120/gp41 interface. The structural information presented here increases our knowledge of CD4- and small molecule-induced conformational changes in Env and the allosteric pathways that lead to membrane fusion
AB - The HIV envelope glycoprotein (Env) trimer undergoes receptor-induced conformational changes that drive fusion of the viral and cellular membranes. Env conformational changes have been observed using low-resolution electron microscopy, but only large-scale rearrangements have been visible. Here, we use hydrogen-deuterium exchange and oxidative labeling to gain a more precise understanding of the unliganded and CD4-bound forms of soluble Env trimers (SOSIP.664), including their glycan composition. CD4 activation induces the reorganization of bridging sheet elements, V1/V2 and V3, much of the gp120 inner domain, and the gp41 fusion subunit. Two CD4 binding site-targeted inhibitors have substantially different effects: NBD-556 partially mimics CD4-induced destabilization of the V1/V2 and V3 crown, whereas BMS-806 only affects regions around the gp120/gp41 interface. The structural information presented here increases our knowledge of CD4- and small molecule-induced conformational changes in Env and the allosteric pathways that lead to membrane fusion
U2 - https://doi.org/10.1016/j.str.2014.05.001
DO - https://doi.org/10.1016/j.str.2014.05.001
M3 - Article
C2 - 24931470
SN - 0969-2126
VL - 22
SP - 974
EP - 984
JO - Structure (London, England
JF - Structure (London, England
IS - 7
ER -