Insights into the structure, correlated motions, and electrostatic properties of two HIV-1 gp120 V3 loops

• Published in: PloS one Vol. 7; no. 11; p. e49925
• Main Authors: López de Victoria, Aliana, Tamamis, Phanourios, Kieslich, Chris A, Morikis, Dimitrios
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19.11.2012; Public Library of Science (PLoS)
• Subjects: Amino Acid Sequence; Analysis; Automation; Binding; Bioengineering; Biology; Bridges (Structures); CCR5 protein; Chemistry; Complementarity; Correlation; Crystal structure; Crystallography; CXCR4 protein; Electrostatic properties; Glycoprotein gp120; Glycoproteins; Health aspects; HIV; HIV Envelope Protein gp120 - chemistry; HIV Envelope Protein gp120 - metabolism; HIV-1 - chemistry; HIV-1 - metabolism; Human immunodeficiency virus; Humans; Hydrogen Bonding; Infections; Medicine; Models, Molecular; Molecular dynamics; Molecular Dynamics Simulation; Mutation; Peptide Fragments - chemistry; Peptide Fragments - metabolism; Physics; Principal components analysis; Receptors, CXCR4 - chemistry; Receptors, CXCR4 - metabolism; Salts; Spatial distribution; Static Electricity; Structural stability; Structure-Activity Relationship; Studies; Trajectories; Viral infections; California
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0049925

The V3 loop of the glycoprotein 120 (gp120) is a contact point for cell entry of HIV-1 leading to infection. Despite sequence variability and lack of specific structure, the highly flexible V3 loop possesses a well-defined role in recognizing and selecting cell-bound coreceptors CCR5 and CXCR4 through a mechanism of charge complementarity. We have performed two independent molecular dynamics (MD) simulations to gain insights into the dynamic character of two V3 loops with slightly different sequences, but significantly different starting crystallographic structures. We have identified highly populated trajectory-specific salt bridges between oppositely charged stem residues Arg9 and Glu25 or Asp29. The two trajectories share nearly identical correlated motions within the simulations, despite their different overall structures. High occupancy salt bridges play a key role in the major cross-correlated motions in both trajectories, and may be responsible for transient structural stability in preparation for coreceptor binding. In addition, the two V3 loops visit conformations with similarities in spatial distributions of electrostatic potentials, despite their inherent flexibility, which may play a role in coreceptor recognition. It is plausible that cooperativity between overall electrostatic potential, charged residue interactions, and correlated motions could be associated with a coreceptor selection and binding.