Book of Abstracts: Albany 2007
June 19-23 2007
The HIV-1 V3 Loop Gives Rise to the Similar Secondary Structures in the HIV-RF and HIV-Thailand Isolates
The conformation of the HIV-RF gp120 V3 loop forming the virus principal neutralizing determinant as well as determinants of cell tropism and syncytium formation, was generated by computer modeling (1) in terms of NMR spectroscopy data (2). The secondary structure of the HIV-RF V3 loop and conformational states of its irregular stretches were determined. Using the analysis of the simulated structure as compared with that of homologous site for the HIV-Thailand isolate (1), the structure elements common for two viral strains were identified. As a result, the following conclusions were drawn based on the data derived: (i) at the N-terminal, the V3-RF loop makes two overlapping β-turns III-III and extended segment, the latter being divided with the C-terminal helix-like region by the structural motif composed of the inverse γ-turn and two consecutive β-turns IV-III; (ii) in the HIV-RF and HIV-Thailand isolates, the fragment of interest constitutes the similar secondary structures, which, in particular, include such structure elements as β-turn III comprising one of the potential sites of the gp120 N-linked glycosylation and the inverse γ-turn residing in the virus immunogenic crest Gly-Pro-Gly; (iii) regardless of local structural differences, about 60% of residues keep their conformational states; the register of these residues comprises Arg-3 critical for utilization of CCR5 co-receptor as well as of heparan sulfate proteoglycans.
The results obtained are at variance with the literature data on the conformational hyper-variability of V3 [see, e.g., review (3)] and point to the possibility of preserving some of its secondary structure elements in diverse HIV-1 isolates. The structurally conservative sites of V3 resulting from these researches are considered to be promising targets for further achievements within the framework of anti-HIV-1 drug and vaccine design projects.
This study was supported by grant from the Belarusian Foundation for Basic Researches (project No X06-020).
References and Footnotes
Alexander M. Andrianov
Institute of Bioorganic Chemistry