AI Article Synopsis
Article Abstract
Viruses have evolved several strategies to modify cellular processes and evade the immune response in order to successfully infect, replicate, and persist in the host. By utilizing in-silico testing of a transmembrane sequence library derived from virus protein sequences, we have pin-pointed a nine amino-acid motif shared by a group of different viruses; this motif resembles the transmembrane domain of the alpha-subunit of the T-cell receptor (TCRalpha). The most striking similarity was found within the immunodeficiency virus (SIV and HIV) glycoprotein 41 TMD (gp41 TMD). Previous studies have shown that stable interactions between TCRalpha and CD3 are localized to this nine amino acid motif within TCRalpha, and a peptide derived from it (TCRalpha TMD, GLRILLLKV) interfered and intervened in the TCR function when added exogenously. We now report that the gp41 TMD peptide co-localizes with CD3 within the TCR complex and inhibits T cell proliferation in vitro. However, the inhibitory mechanism of gp41 TMD differs from that of the TCRalpha TMD and also from the other two known immunosuppressive regions within gp41.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2932719 | PMC |
| http://dx.doi.org/10.1371/journal.ppat.1001085 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Hybrids of small CD4 mimics and gp41-related peptides as dual-target HIV entry inhibitors.
Bioorg Med Chem
December 2022
Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU), 2-3-10 Kandasurugadai, Chiyoda-ku, Tokyo 101-0062, Japan. Electronic address:
Hybrid molecules containing small CD4 mimics and gp41-C-terminal heptad repeat (CHR)-related peptides have been developed. A YIR-821 derivative was adopted as a CD4 mimic, which inhibits the interaction of gp120 with CD4. SC-peptides, SC34 and SC22EK, were also used as CHR-related peptides, which inhibit the interaction between the N-terminal heptad repeat (NHR) and CHR and thereby membrane fusion.
View Article and Find Full Text PDFMolecular recognition of a membrane-anchored HIV-1 pan-neutralizing epitope.
Commun Biol
November 2022
Instituto Biofisika (CSIC-UPV/EHU), University of the Basque Country (UPV/EHU), PO Box 644, 48080, Bilbao, Spain.
Antibodies against the carboxy-terminal section of the membrane-proximal external region (C-MPER) of the HIV-1 envelope glycoprotein (Env) are considered as nearly pan-neutralizing. Development of vaccines capable of producing analogous broadly neutralizing antibodies requires deep understanding of the mechanism that underlies C-MPER recognition in membranes. Here, we use the archetypic 10E8 antibody and a variety of biophysical techniques including single-molecule approaches to study the molecular recognition of C-MPER in membrane mimetics.
View Article and Find Full Text PDFRotational Dynamics of The Transmembrane Domains Play an Important Role in Peptide Dynamics of Viral Fusion and Ion Channel Forming Proteins-A Molecular Dynamics Simulation Study.
Viruses
March 2022
Institute of Biophotonics, College of Biomedical Science and Engineering, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan.
Focusing on the transmembrane domains (TMDs) of viral fusion and channel-forming proteins (VCPs), experimentally available and newly generated peptides in an ideal conformation of the S and E proteins of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and SARS-CoV, gp41 and Vpu, both of human immunodeficiency virus type 1 (HIV-1), haemagglutinin and M2 of influenza A, as well as gB of herpes simplex virus (HSV), are embedded in a fully hydrated lipid bilayer and used in multi-nanosecond molecular dynamics simulations. It is aimed to identify differences in the dynamics of the individual TMDs of the two types of viral membrane proteins. The assumption is made that the dynamics of the individual TMDs are decoupled from their extra-membrane domains, and that the mechanics of the TMDs are distinct from each other due to the different mechanism of function of the two types of proteins.
View Article and Find Full Text PDFCholesterol-Mediated Clustering of the HIV Fusion Protein gp41 in Lipid Bilayers.
J Mol Biol
January 2022
Department of Chemistry, Massachusetts Institute of Technology, 170 Albany Street, Cambridge, MA 02139, United States. Electronic address: https://twitter.com/MeiHongLab.
The envelope glycoprotein (Env) of the human immunodeficient virus (HIV-1) is known to cluster on the viral membrane surface to attach to target cells and cause membrane fusion for HIV-1 infection. However, the molecular structural mechanisms that drive Env clustering remain opaque. Here, we use solid-state NMR spectroscopy and molecular dynamics (MD) simulations to investigate nanometer-scale clustering of the membrane-proximal external region (MPER) and transmembrane domain (TMD) of gp41, the fusion protein component of Env.
View Article and Find Full Text PDFInteractions of HIV gp41's membrane-proximal external region and transmembrane domain with phospholipid membranes from P NMR.
Biochim Biophys Acta Biomembr
November 2021
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address:
HIV-1 entry into cells requires coordinated changes of the conformation and dynamics of both the fusion protein, gp41, and the lipids in the cell membrane and virus envelope. Commonly proposed features of membrane deformation during fusion include high membrane curvature, lipid disorder, and membrane surface dehydration. The virus envelope and target cell membrane contain a diverse set of phospholipids and cholesterol.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!