Book of Abstracts: Albany 2009

category image Albany 2009
Conversation 16
June 16-20 2009
© Adenine Press (2008)

Common Structural Motifs of the HIV-1 V3 Variable Loops As the Weak Units in the Virus Protection System

The computational approaches that combined the NMR-based protein structure modeling with the mathematical statistics methods were used to define the locally accurate 3D structures of the HIV-1 gp120 V3 loops from Minnesota, Haiti, RF, and Thailand isolates in water solution as well as from Minnesota and Haiti isolates in a water/trifluoroethanol mixed solvent. To specify the structural motifs of V3 giving rise to the close spatial folds regardless of the sequence and environment variability, the simulated structures and their individual segments of different length were collated between themselves and with those derived previously from homology modeling (1) and X-ray crystallography (2). As a result, the sequence and environment changes were found to trigger the considerable structural rearrangements of the V3 loop, but, at the same time, some of the functionally crucial V3 stretches were shown to keep the 3D shapes in all the cases in question. In the first place, it concerns core V3 sequence 15-20 as well as its N- and C-terminal sites 3-7 and 28-32 comprising the residues, which contribute significantly to the virus immunogenicity and cell tropism. In addition, structurally rigid V3 stretch 3-7 includes the highly conservative glycolysation site of gp120 utilized by the virus for defense against neutralizing antibodies and elevation of its infectivity. In the context of these findings, the inflexible V3 motifs identified in the present study may present the Achilles' heel in the HIV-1 protection system and, therefore, their detection is of great importance to successful design of the V3-based anti-AIDS drugs able to stop the HIV's spread.

This study was supported by grants from the Union State of Russia and Belarus (scientific program SKIF-GRID; No. 4U-S/07-111) as well as from the Belarusian Foundation for Basic Research (project X08-003).

References and Footnotes
  1. I.V.Anishchenko and A.M. Andrianov, Proceedings of II International Conference "Advanced Information and Telemedicine Technologies for Health" (Minsk, 2008), 12-16 (2008).
  2. C.C. Huang, M. Tang, M.Y. Zhang, S. Majeed, E. Montabana, R.L. Stanfield, D.S. Dimitrov, B. Korber, J. Sodroski, I.A. Wilson, R. Wyatt and P.D. Kwong, Science.310, 1025 ? 1028 (2005).

Alexander M. Andrianov1
Ivan V. Anishchenko2

1Inst. of Bioorganic Chemistry
Nat'l Academy of Sciences of Belarus
Kuprevich Street 5/2
220141 Minsk, Rep. of Belarus
2United Inst. of Informatics Problems
Nat'l Academy of Sciences of Belarus
Surganov Street 6
220012 Minsk, Rep. of Belarus