TY - JOUR
T1 - Human immunodeficiency virus type 1 Vpr
T2 - Oligomerization is an essential feature for its incorporation into virus particles
AU - Venkatachari, Narasimhan J.
AU - Walker, Leah A.
AU - Tastan, Oznur
AU - Le, Thien
AU - Dempsey, Timothy M.
AU - Li, Yaming
AU - Yanamala, Naveena
AU - Srinivasan, Alagarsamy
AU - Klein-Seetharaman, Judith
AU - Montelaro, Ronald C.
AU - Ayyavoo, Velpandi
N1 - Funding Information:
This work was supported in part by the grant GM082251 from the NIAID, NIH.
PY - 2010
Y1 - 2010
N2 - HIV-1 Vpr, a nonstructural viral protein associated with virus particles, has a positive role in the efficient transport of PIC into the nucleus of non-dividing target cells and enhances virus replication in primary T cells. Vpr is a 96 amino acid protein and the structure by NMR shows three helical domains. Vpr has been shown to exist as dimers and higher order oligomers. Considering the multifunctional nature of Vpr, the contribution of distinct helical domains to the dimer/oligomer structure of Vpr and the relevance of this feature to its functions are not clear. To address this, we have utilized molecular modeling approaches to identify putative models of oligomerization. The predicted interface residues were subjected to site-directed mutagenesis and evaluated their role in intermolecular interaction and virion incorporation. The interaction between Vpr molecules was monitored by Bimolecular Fluorescence complementation (BiFC) method. The results show that Vpr forms oligomers in live cells and residues in helical domains play critical roles in oligomerization. Interestingly, Vpr molecules defective in oligomerization also fail to incorporate into the virus particles. Based on the data, we suggest that oligomerization of Vpr is essential for virion incorporation property and may also have a role in the events associated with virus infection.
AB - HIV-1 Vpr, a nonstructural viral protein associated with virus particles, has a positive role in the efficient transport of PIC into the nucleus of non-dividing target cells and enhances virus replication in primary T cells. Vpr is a 96 amino acid protein and the structure by NMR shows three helical domains. Vpr has been shown to exist as dimers and higher order oligomers. Considering the multifunctional nature of Vpr, the contribution of distinct helical domains to the dimer/oligomer structure of Vpr and the relevance of this feature to its functions are not clear. To address this, we have utilized molecular modeling approaches to identify putative models of oligomerization. The predicted interface residues were subjected to site-directed mutagenesis and evaluated their role in intermolecular interaction and virion incorporation. The interaction between Vpr molecules was monitored by Bimolecular Fluorescence complementation (BiFC) method. The results show that Vpr forms oligomers in live cells and residues in helical domains play critical roles in oligomerization. Interestingly, Vpr molecules defective in oligomerization also fail to incorporate into the virus particles. Based on the data, we suggest that oligomerization of Vpr is essential for virion incorporation property and may also have a role in the events associated with virus infection.
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U2 - 10.1186/1743-422X-7-119
DO - 10.1186/1743-422X-7-119
M3 - Article
C2 - 20529298
AN - SCOPUS:77953055741
SN - 1743-422X
VL - 7
JO - Virology Journal
JF - Virology Journal
M1 - 119
ER -