The Influence of N-Linked Glycans on the MolecularDynamics of the HIV-1 gp120 V3 Loop
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Date
2013
Journal Title
Journal ISSN
Volume Title
Publisher
PLoS ONE
Abstract
N-linked glycans attached to specific amino acids of the gp120 envelope trimer of a HIV virion can modulate the binding
affinity of gp120 to CD4, influence coreceptor tropism, and play an important role in neutralising antibody responses.
Because of the challenges associated with crystallising fully glycosylated proteins, most structural investigations have
focused on describing the features of a non-glycosylated HIV-1 gp120 protein. Here, we use a computational approach to
determine the influence of N-linked glycans on the dynamics of the HIV-1 gp120 protein and, in particular, the V3 loop. We
compare the conformational dynamics of a non-glycosylated gp120 structure to that of two glycosylated gp120 structures,
one with a single, and a second with five, covalently linked high-mannose glycans. Our findings provide a clear illustration of
the significant effect that N-linked glycosylation has on the temporal and spatial properties of the underlying protein
structure. We find that glycans surrounding the V3 loop modulate its dynamics, conferring to the loop a marked propensity
towards a more narrow conformation relative to its non-glycosylated counterpart. The conformational effect on the V3 loop
provides further support for the suggestion that N-linked glycosylation plays a role in determining HIV-1 coreceptor
tropism.
Description
Keywords
N-linked glycans, gp120 envelope trimer, gp120, HIV-1 gp120 V3 Loop
Citation
Wood, N.T. et al. (2013) The Influence of N-Linked Glycans on the Molecular Dynamics of the HIV-1 gp120 V3 Loop. PLoS ONE, 8(11): 1-9