title: Interaction of the HIV-1 gp120 viral protein V3 loop with bacterial lipopolysaccharide: a pattern recognition inhibition.
abstract: HIV-1 represents an elusive target for therapeutic compounds due to its high rate of mutation. Targeting structural patterns instead of a constantly changing specific three-dimensional structure may represent an approach that is less sensitive to viral mutations. The V3 loop of gp120 of HIV-1, which is responsible for binding of viral gp120 to CCR5 or CXCR4 coreceptors, has already been identified as an effective target for the inhibition of viral entry. The peptide derived from the V3 loop of gp120 specifically interacts with the lipid A moiety of LPS, as does the full gp120 protein. NMR analysis of V3 in complex with LPS shows formation of an amphipathic turn. The interaction between LPS and V3 relies on the structural pattern, comprising a combination of hydrophobic and charge interactions, similar to the interaction between antimicrobial peptides and LPS. LPS inhibited binding of gp120 to the surface of target T cells. Nonendotoxic LPS antagonists inhibited viral infection, demonstrating the possibility for the development of an inhibitor of HIV-1 attachment to T cells based on the recognition of a conserved structural pattern.
authors.affiliation: Department of Biotechnology, National Institute of Chemistry, 1000 Ljubljana, Slovenia.
authors.forename: Andreja
authors.initials: A
authors.lastname: Majerle
authors.forename: Primoz
authors.initials: P
authors.lastname: Pristovsek
authors.forename: Mateja
authors.initials: M
authors.lastname: Mancek-Keber
authors.forename: Roman
authors.initials: R
authors.lastname: Jerala
mesh_terms: D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000378:metabolism / Q000494:pharmacology; D057809:HEK293 Cells; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation; D015728:Receptors, HIV / Q000378:metabolism; D012475:Salmonella / Q000737:chemistry*; D013379:Substrate Specificity; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D053585:Virus Attachment / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D015699:HIV Envelope Protein gp120; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D015728:Receptors, HIV; C514793:gp120 protein, Human immunodeficiency virus 1