This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Boutonnet, N. Articles by Lasters, I. Search for Related Content PubMed PubMed Citation Articles by Boutonnet, N. Articles by Lasters, I.

 Previous Article  |  Next Article 

Journal of Virology, August 2002, p. 7595-7606, Vol. 76, No. 15
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.15.7595-7606.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Comparison of Predicted Scaffold-Compatible Sequence Variation in the Triple-Hairpin Structure of Human Immunodeficiency Virus Type 1 gp41 with Patient Data

Nathalie Boutonnet,¹ Wouter Janssens,² Carlo Boutton,¹ Jean-Luc Verschelde,¹ Leo Heyndrickx,² Els Beirnaert,² Guido van der Groen,² and Ignace Lasters^1*

Algonomics NV, 9052 Ghent,¹ Unit of Virology, Department of Microbiology, Institute of Tropical Medicine, 2000 Antwerp, Belgium²

Received 26 October 2001/ Accepted 26 April 2002

It has been proposed that the ectodomain of human immunodeficiency virus type 1 (HIV-1) gp41 (e-gp41), involved in HIV entry into the target cell, exists in at least two conformations, a pre-hairpin intermediate and a fusion-active hairpin structure. To obtain more information on the structure-sequence relationship in e-gp41, we performed in silico a full single-amino-acid substitution analysis, resulting in a Fold Compatible Database (FCD) for each conformation. The FCD contains for each residue position in a given protein a list of values assessing the energetic compatibility (ECO) of each of the 20 natural amino acids at that position. Our results suggest that FCD predictions are in good agreement with the sequence variation observed for well-validated e-gp41 sequences. The data show that at a minECO threshold value of 5 kcal/mol, about 90% of the observed patient sequence variation is encompassed by the FCD predictions. Some inconsistent FCD predictions at N-helix positions packing against residues of the C helix suggest that packing of both peptides may involve some flexibility and may be attributed to an altered orientation of the C-helical domain versus the N-helical region. The permissiveness of sequence variation in the C helices is in agreement with FCD predictions. Comparison of N-core and triple-hairpin FCDs suggests that the N helices may impose more constraints on sequence variation than the C helices. Although the observed sequences of e-gp41 contain many multiple mutations, our method, which is based on single-point mutations, can predict the natural sequence variability of e-gp41 very well.

---

* Corresponding author. Mailing address: AlgoNomics NV, Technologiepark 4, 9052 Ghent-Zwijnaarde, Belgium. Phone: 32-9-2411100. Fax: 32-9-2411102. E-mail: Ignace.Lasters{at}algonomics.com.

---

Journal of Virology, August 2002, p. 7595-7606, Vol. 76, No. 15
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.15.7595-7606.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• O'Rourke, S. M., Schweighardt, B., Scott, W. G., Wrin, T., Fonseca, D. P. A. J., Sinangil, F., Berman, P. W. (2009). Novel Ring Structure in the gp41 Trimer of Human Immunodeficiency Virus Type 1 That Modulates Sensitivity and Resistance to Broadly Neutralizing Antibodies. J. Virol. 83: 7728-7738 [Abstract] [Full Text]