Structural dynamics of HIV-1 envelope GP120 outer domain with V3 loop

Citations of this article
Mendeley users who have this article in their library.


BACKGROUND: The net charge of the hypervariable V3 loop on the HIV-1 envelope gp120 outer domain plays a key role in modulating viral phenotype. However, the molecular mechanisms underlying the modulation remain poorly understood.<br /><br />METHODOLOGY/PRINCIPAL FINDINGS: By combining computational and experimental approaches, we examined how V3 net charge could influence the phenotype of the gp120 interaction surface. Molecular dynamics simulations of the identical gp120 outer domain, carrying a V3 loop with net charge of +3 or +7, showed that the V3 change alone could induce global changes in fluctuation and conformation of the loops involved in binding to CD4, coreceptor and antibodies. A neutralization study using the V3 recombinant HIV-1 infectious clones showed that the virus carrying the gp120 with +3 V3, but not with +7 V3, was resistant to neutralization by anti-CD4 binding site monoclonal antibodies. An information entropy study shows that otherwise variable surface of the gp120 outer domain, such as V3 and a region around the CD4 binding loop, are less heterogeneous in the gp120 subpopulation with +3 V3.<br /><br />CONCLUSIONS/SIGNIFICANCE: These results suggest that the HIV-1 gp120 V3 loop acts as an electrostatic modulator that influences the global structure and diversity of the interaction surface of the gp120 outer domain. Our findings will provide a novel structural basis to understand how HIV-1 adjusts relative replication fitness by V3 mutations.




Yokoyama, M., Naganawa, S., Yoshimura, K., Matsushita, S., & Sato, H. (2012). Structural dynamics of HIV-1 envelope GP120 outer domain with V3 loop. PLoS ONE, 7(5).

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free