3rd Conference on Retroviruses and Opportunistic Infections Washington, DC - January 28-February 1, 1996

Conf Retroviruses Opportunistic Infect 1996 Jan 28-Feb 1; 3rd:61 (abstract no. 48)

Srinivasan A¹, Mahalingam S¹, Murali R², Collman RG², Patel M¹, Serio D^1
1 Thomas Jefferson University, ² University of Pennsylvania, Philadelphia

HIV-1 Vpr sequences were analyzed for secondary structure elements by neural networks and sequence profile. Further, Vpr sequences were compared with protein structures that have been determined by X-ray crystallography and NMR from Brookhaven data base (NrL3d) using BLAST. These methods have indicated that the Vpr molecule contains helical domains. We have recently obtained evidence in support of this by CD spectroscopy. Based on the information obtained from severalcalculations, a model was built for Vpr using Quanta (Polygen Corporation, Waltham, MA). The model contains two major helices HI(7-29) and HII (49-62) present in the same area also identified by prediction. The molecule is stabilized by dipole-dipole interactions between HI and HII. The flexible part connecting the two helices is further reinforced by a hydrophobic pocket formed by 30Ala, 31Val, 34Phe, 35Pro and 37Ile. Mutations involving substitutions, insertions, and deletions of amino acids in Vpr were evaluated for expression, virion incorporation, nuclear localization, oligomerization and biological functions. Substitution of amino acids in the predicted helical domains revealed that the helical domains play a major role in Vpr functions. Vpr containing only amino acids 1-72 showed virion incorporation phenotype indicating that the C-terminus is not essential for this function. However, the C-terminus contributes to the stability of Vpr. The results obtained with Vpr containing mutations throughout the molecule shed light on the interrelationship between oligomerization, nuclear localization, virion incorporation, and biological effects of Vpr.

960128
48

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