Peer-Reviewed Journal Details
Mandatory Fields
Wood, NT;Fadda, E;Davis, R;Grant, OC;Martin, JC;Woods, RJ;Travers, SA
2013
November
PLoS ONE
The Influence of N-Linked Glycans on the Molecular Dynamics of the HIV-1 gp120 V3 Loop
Published
22 ()
Optional Fields
IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE GLYCOPROTEIN GP120 AMINO-ACID SUBSTITUTION HAMSTER OVARY CELLS CORECEPTOR USAGE ANTIBODY NEUTRALIZATION MONOCLONAL-ANTIBODIES SOLUBLE CD4 CONFORMATIONAL DYNAMICS PHENOTYPE PREDICTION
8
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.
SAN FRANCISCO
1932-6203
10.1371/journal.pone.0080301
Grant Details