This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
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 Lu, M.
Right arrow Articles by Shen, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lu, M.
Right arrow Articles by Shen, S.

 Previous Article  |  Next Article 

Journal of Virology, May 1999, p. 4433-4438, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Subdomain Folding and Biological Activity of the Core Structure from Human Immunodeficiency Virus Type 1 gp41: Implications for Viral Membrane Fusion

Min Lu,* Hong Ji, and Steven Shen

Department of Biochemistry, Weill Medical College of Cornell University, New York, New York 10021

Received 9 September 1998/Accepted 5 January 1999

The envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) consists of two subunits, gp120 and gp41. The extraviral portion (ectodomain) of gp41 contains an alpha -helical domain that likely represents the core of the fusion-active conformation of the molecule. Here we report the identification and characterization of a minimal, autonomous folding subdomain that retains key determinants in specifying the overall fold of the gp41 ectodomain core. This subdomain, designated N34(L6)C28, is formed by covalent attachment of peptides N-34 and C-28 by a short flexible linker in place of the normal disulfide-bonded loop sequence. N34(L6)C28 forms a highly thermostable, alpha -helical trimer. Point mutations within the envelope protein complex that abolish membrane fusion and HIV-1 infectivity also impede the formation of the N34(L6)C28 core. Moreover, N34(L6)C28 is capable of inhibiting HIV-1 envelope-mediated membrane fusion. Taken together, these results indicate that the N34(L6)C28 core plays a direct role in the membrane fusion step of HIV-1 infection and thus provides a molecular target for the development of antiviral pharmaceutical agents.

* Corresponding author. Mailing address: Department of Biochemistry, Weill Medical College of Cornell University, 1300 York Ave., New York, NY 10021. Phone: (212) 746-6562. Fax: (212) 746-8875. E-mail: mlu{at}mail.med.cornell.edu.

Journal of Virology, May 1999, p. 4433-4438, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Eggink, D., Langedijk, J. P. M., Bonvin, A. M. J. J., Deng, Y., Lu, M., Berkhout, B., Sanders, R. W. (2009). Detailed Mechanistic Insights into HIV-1 Sensitivity to Three Generations of Fusion Inhibitors. J. Biol. Chem. 284: 26941-26950 [Abstract] [Full Text]  
  • He, Y., Liu, S., Jing, W., Lu, H., Cai, D., Chin, D. J., Debnath, A. K., Kirchhoff, F., Jiang, S. (2007). Conserved Residue Lys574 in the Cavity of HIV-1 Gp41 Coiled-coil Domain Is Critical for Six-helix Bundle Stability and Virus Entry. J. Biol. Chem. 282: 25631-25639 [Abstract] [Full Text]  
  • Huang, J.-H., Lu, L., Lu, H., Chen, X., Jiang, S., Chen, Y.-H. (2007). Identification of the HIV-1 gp41 Core-binding Motif in the Scaffolding Domain of Caveolin-1. J. Biol. Chem. 282: 6143-6152 [Abstract] [Full Text]  
  • Suntoke, T. R., Chan, D. C. (2005). The Fusion Activity of HIV-1 gp41 Depends on Interhelical Interactions. J. Biol. Chem. 280: 19852-19857 [Abstract] [Full Text]  
  • Trivedi, V. D., Cheng, S.-F., Wu, C.-W., Karthikeyan, R., Chen, C.-J., Chang, D.-K. (2003). The LLSGIV stretch of the N-terminal region of HIV-1 gp41 is critical for binding to a model peptide, T20. Protein Eng Des Sel 16: 311-317 [Abstract] [Full Text]  
  • Sanders, R. W., Vesanen, M., Schuelke, N., Master, A., Schiffner, L., Kalyanaraman, R., Paluch, M., Berkhout, B., Maddon, P. J., Olson, W. C., Lu, M., Moore, J. P. (2002). Stabilization of the Soluble, Cleaved, Trimeric Form of the Envelope Glycoprotein Complex of Human Immunodeficiency Virus Type 1. J. Virol. 76: 8875-8889 [Abstract] [Full Text]  
  • Boutonnet, N., Janssens, W., Boutton, C., Verschelde, J.-L., Heyndrickx, L., Beirnaert, E., van der Groen, G., Lasters, I. (2002). Comparison of Predicted Scaffold-Compatible Sequence Variation in the Triple-Hairpin Structure of Human Immunodeficiency Virus Type 1 gp41 with Patient Data. J. Virol. 76: 7595-7606 [Abstract] [Full Text]  
  • Follis, K. E., Larson, S. J., Lu, M., Nunberg, J. H. (2002). Genetic Evidence that Interhelical Packing Interactions in the gp41 Core Are Critical for Transition of the Human Immunodeficiency Virus Type 1 Envelope Glycoprotein to the Fusion-Active State. J. Virol. 76: 7356-7362 [Abstract] [Full Text]  
  • Liu, J., Wang, S., Hoxie, J. A., LaBranche, C. C., Lu, M. (2002). Mutations That Destabilize the gp41 Core Are Determinants for Stabilizing the Simian Immunodeficiency Virus-CPmac Envelope Glycoprotein Complex. J. Biol. Chem. 277: 12891-12900 [Abstract] [Full Text]  
  • Lu, M., Stoller, M. O., Wang, S., Liu, J., Fagan, M. B., Nunberg, J. H. (2001). Structural and Functional Analysis of Interhelical Interactions in the Human Immunodeficiency Virus Type 1 gp41 Envelope Glycoprotein by Alanine-Scanning Mutagenesis. J. Virol. 75: 11146-11156 [Abstract] [Full Text]  
  • Krueger, D. K., Kelly, S. M., Lewicki, D. N., Ruffolo, R., Gallagher, T. M. (2001). Variations in Disparate Regions of the Murine Coronavirus Spike Protein Impact the Initiation of Membrane Fusion. J. Virol. 75: 2792-2802 [Abstract] [Full Text]  
  • Sanders, R. W., Schiffner, L., Master, A., Kajumo, F., Guo, Y., Dragic, T., Moore, J. P., Binley, J. M. (2000). Variable-Loop-Deleted Variants of the Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Can Be Stabilized by an Intermolecular Disulfide Bond between the gp120 and gp41 Subunits. J. Virol. 74: 5091-5100 [Abstract] [Full Text]  
  • Weng, Y., Yang, Z., Weiss, C. D. (2000). Structure-Function Studies of the Self-Assembly Domain of the Human Immunodeficiency Virus Type 1 Transmembrane Protein gp41. J. Virol. 74: 5368-5372 [Abstract] [Full Text]  
  • Shu, W., Ji, H., Lu, M. (2000). Interactions between HIV-1 gp41 Core and Detergents and Their Implications for Membrane Fusion. J. Biol. Chem. 275: 1839-1845 [Abstract] [Full Text]  
  • Ji, H., Shu, W., Burling, F. T., Jiang, S., Lu, M. (1999). Inhibition of Human Immunodeficiency Virus Type 1 Infectivity by the gp41 Core: Role of a Conserved Hydrophobic Cavity in Membrane Fusion. J. Virol. 73: 8578-8586 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»