This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Stanley, B. J.
Right arrow Articles by Xiong, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Stanley, B. J.
Right arrow Articles by Xiong, Y.

 Previous Article  |  Next Article 

Journal of Virology, September 2008, p. 8656-8663, Vol. 82, No. 17
0022-538X/08/$08.00+0     doi:10.1128/JVI.00767-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Structural Insight into the Human Immunodeficiency Virus Vif SOCS Box and Its Role in Human E3 Ubiquitin Ligase Assembly{triangledown} ,{dagger}

Bradford J. Stanley,1 Elana S. Ehrlich,2 Leslie Short,1 Yunkai Yu,2 Zuoxiang Xiao,2 Xiao-Fang Yu,2* and Yong Xiong1*

Department of Molecular Biophysics and Biochemistry, Yale University, P.O. Box 208114, New Haven, Connecticut 06510,1 Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 212052

Received 8 April 2008/ Accepted 10 June 2008

Human immunodeficiency virus (HIV) virion infectivity factor (Vif) causes the proteasome-mediated destruction of human antiviral protein APOBEC3G by tethering it to a cellular E3 ubiquitin ligase composed of ElonginB, ElonginC, Cullin5, and Rbx2. It has been proposed that HIV Vif hijacks the E3 ligase through two regions within its C-terminal domain: a BC box region that interacts with ElonginC and a novel zinc finger motif that interacts with Cullin5. We have determined the crystal structure of the HIV Vif BC box in complex with human ElonginB and ElonginC. This complex presents direct structural evidence of the recruitment of a human ubiquitin ligase by a viral BC box protein that mimics the conserved interactions of cellular ubiquitin ligases. We further mutated conserved hydrophobic residues in a region downstream of the Vif BC box. These mutations demonstrate that this region, the Vif Cullin box, composes a third E3-ligase recruiting site critical for interaction between Vif and Cullin5. Furthermore, our homology modeling reveals that the Vif Cullin box and zinc finger motif may be positioned adjacent to the N terminus of Cullin5 for interaction with loop regions in the first cullin repeat of Cullin5.

* Corresponding authors. Mailing address for Y. Xiong: Department of Molecular Biophysics and Biochemistry, Yale University, P.O. Box 208114, New Haven, CT 06520-8114. Phone: (203) 436-2608. Fax: (203) 432-1296. E-mail: yong.xiong{at}yale.edu. Mailing address for X.-F. Yu: Department of Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St., Baltimore, MD 21205. Phone: (410) 955-3768. Fax: (410) 614-8263. E-mail: xfyu{at}jhsph.edu

{triangledown} Published ahead of print on 18 June 2008.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, September 2008, p. 8656-8663, Vol. 82, No. 17
0022-538X/08/$08.00+0     doi:10.1128/JVI.00767-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Iwatani, Y., Chan, D. S. B., Liu, L., Yoshii, H., Shibata, J., Yamamoto, N., Levin, J. G., Gronenborn, A. M., Sugiura, W. (2009). HIV-1 Vif-mediated ubiquitination/degradation of APOBEC3G involves four critical lysine residues in its C-terminal domain. Proc. Natl. Acad. Sci. USA 106: 19539-19544 [Abstract] [Full Text]  
  • Chen, G., He, Z., Wang, T., Xu, R., Yu, X.-F. (2009). A Patch of Positively Charged Amino Acids Surrounding the Human Immunodeficiency Virus Type 1 Vif SLVx4Yx9Y Motif Influences Its Interaction with APOBEC3G. J. Virol. 83: 8674-8682 [Abstract] [Full Text]  
  • Reingewertz, T. H., Benyamini, H., Lebendiker, M., Shalev, D. E., Friedler, A. (2009). The C-terminal domain of the HIV-1 Vif protein is natively unfolded in its unbound state. Protein Eng Des Sel 22: 281-287 [Abstract] [Full Text]  
  • Pery, E., Rajendran, K. S., Brazier, A. J., Gabuzda, D. (2009). Regulation of APOBEC3 Proteins by a Novel YXXL Motif in Human Immunodeficiency Virus Type 1 Vif and Simian Immunodeficiency Virus SIVagm Vif. J. Virol. 83: 2374-2381 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»