Coevolution analysis of HIV-1 envelope glycoprotein complex

Reda Rawi, Khalid Kunji, Abdelali Haoudi, Halima Bensmail

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The HIV-1 Env spike is the main protein complex that facilitates HIV-1 entry into CD4+ host cells. HIV-1 entry is a multistep process that is not yet completely understood. This process involves several protein-protein interactions between HIV-1 Env and a variety of host cell receptors along with many conformational changes within the spike. HIV-1 Env developed due to high mutation rates and plasticity escape strategies from immense immune pressure and entry inhibitors. We applied a coevolution and residue-residue contact detecting method to identify coevolution patterns within HIV-1 Env protein sequences representing all group M subtypes. We identified 424 coevolving residue pairs within HIV-1 Env. The majority of predicted pairs are residue-residue contacts and are proximal in 3D structure. Furthermore, many of the detected pairs have functional implications due to contributions in either CD4 or coreceptor binding, or variable loop, gp120-gp41, and interdomain interactions. This study provides a new dimension of information in HIV research. The identified residue couplings may not only be important in assisting gp120 and gp41 coordinate structure prediction, but also in designing new and effective entry inhibitors that incorporate mutation patterns of HIV-1 Env.

Original languageEnglish
Article number0143245
JournalPLoS One
Volume10
Issue number11
DOIs
Publication statusPublished - 1 Nov 2015

Fingerprint

coevolution
Human immunodeficiency virus 1
HIV-1
glycoproteins
Glycoproteins
env Gene Products
Proteins
Plasticity
mutation
protein-protein interactions
Mutation Rate
amino acid sequences
HIV
cells
Pressure
Mutation
receptors
prediction
Research

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Coevolution analysis of HIV-1 envelope glycoprotein complex. / Rawi, Reda; Kunji, Khalid; Haoudi, Abdelali; Bensmail, Halima.

In: PLoS One, Vol. 10, No. 11, 0143245, 01.11.2015.

Research output: Contribution to journalArticle

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