Details

Autor(en) / Beteiligte

• Lemmin, Thomas
• Soto, Cinque
• Stuckey, Jonathan
• Kwong, Peter D.

Titel

Microsecond Dynamics and Network Analysis of the HIV-1 SOSIP Env Trimer Reveal Collective Behavior and Conserved Microdomains of the Glycan Shield

Ist Teil von

• Structure (London), 2017-10, Vol.25 (10), p.1631-1639.e2

Ort / Verlag

United States: Elsevier Ltd

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• The trimeric HIV-1-envelope (Env) spike is one of the most glycosylated protein complexes known, with roughly half its mass comprising host-derived N-linked glycan. Here we use molecular dynamics to provide insight into its structural dynamics and into how both protomer and glycan movements coordinate to shield the Env protein surface. A 2-μs molecular dynamics simulation of a fully glycosylated atomistic model of the HIV-1 SOSIP Env trimer revealed a spectrum of protomer-scissoring and trimer-opening movements. Network analysis showed that highly conserved glycans combined with protomer scissoring to restrict access to the binding site of the CD4 receptor. The network property of betweenness centrality appeared to identify whether glycans spread to restrict access or cluster to maintain the high-mannose character of the shield. We also observed stable microdomains comprising patches of glycan, with neutralizing antibodies generally binding at the interface between glycan microdomains. Overall, our results provide a microsecond-based understanding of the Env glycan shield. [Display omitted] •2-μs molecular dynamics simulation of the fully glycosylated HIV-1 SOSIP Env trimer•Env protomers undergo scissoring movements, which induce trimer asymmetry•Glycans form microdomains, which remained stable at the microsecond timescale•Neutralizing antibodies recognize interfaces between glycan microdomains Lemmin et al. employed an all-atom molecular dynamics simulation on the microsecond timescale of a fully glycosylated HIV-1 SOSIP Env trimer to investigate the dynamics of its glycan shield. Their analyses provide a submicrosecond dynamics-based understanding of the collective behavior of glycans on the HIV trimer.