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  • Meeting abstract
  • Open Access

Comparative structural analysis of retroviral fusion proteins identifies regions that modulate membrane fusion: a potential retroviral achilles heal?

  • Daniel Lamb1,
  • Alexander W Schüttelkopf2,
  • Daan M F van Aalten2 and
  • David W Brighty1Email author
Retrovirology20118(Suppl 1):A163

https://doi.org/10.1186/1742-4690-8-S1-A163

Published: 6 June 2011

Keywords

Fusion ProteinAsparagineMembrane FusionPeptide InhibitorBovine Leukaemia Virus

Refolding of viral class-1 membrane fusion proteins from a native state to a trimer-of-hairpins structure promotes entry of viruses into cells. Here we present the structure of the bovine leukaemia virus transmembrane glycoprotein (TM) and identify a group of asparagine residues at the membrane-distal end of the trimer of hairpins that is strikingly conserved among divergent viruses. These asparagines are not essential for surface display of pre-fusogenic envelope. Instead, substitution of these residues dramatically disrupts membrane fusion. Our data indicate that through electrostatic interactions with of a chloride ion the asparagine residues promote assembly and profoundly stabilize the fusion-active structures that are required for viral envelope-mediated membrane fusion. Moreover, the BLV TM structure also reveals a charge-surrounded hydrophobic pocket on the central coiled coil and interactions with basic residues that cluster around this pocket are critical to membrane fusion and form a target for peptide inhibitors of envelope function. Charge-surrounded pockets and electrostatic interactions with small ions are common leitmotifs among class-1 fusion proteins. We will discuss the impact of these observations in light of current models of membrane fusion and as potential targets for therapeutic inhibition of viral entry.

Authors’ Affiliations

(1)
The Biomedical Research Institute, College of Medicine, Ninewells Hospital, University, Dundee, Scotland, UK
(2)
Division of Molecular Microbiology, College of Life Sciences, University of Dundee, Dundee, UK

Copyright

© Lamb et al; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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