Next Article in Journal
Molecular Modeling of Prion Transmission to Humans
Next Article in Special Issue
From Crescent to Mature Virion: Vaccinia Virus Assembly and Maturation
Previous Article in Journal
Prion Protein-Specific Antibodies-Development, Modes of Action and Therapeutics Application
Previous Article in Special Issue
Assembly and Maturation of a T = 4 Quasi-Equivalent Virus Is Guided by Electrostatic and Mechanical Forces
Article Menu

Export Article

Open AccessArticle
Viruses 2014, 6(10), 3738-3765; doi:10.3390/v6103738

Mutation of the Highly Conserved Ser-40 of the HIV-1 p6 Gag Protein to Phe Causes the Formation of a Hydrophobic Patch, Enhances Membrane Association, and Polyubiquitination of Gag

1
Institute of Virology, Friedrich-Alexander-University, 91054 Erlangen, Germany
2
Department of Chemistry and Centre for Pharmacy, University of Bergen, N-5007 Bergen, Norway
3
Institute of Biochemistry, Charité Universitätsmedizin-Berlin, 10117 Berlin, Germany
Current Address: Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112-5650, USA.
*
Author to whom correspondence should be addressed.
Received: 6 August 2014 / Revised: 19 September 2014 / Accepted: 26 September 2014 / Published: 2 October 2014
(This article belongs to the Special Issue Virus Maturation)
View Full-Text   |   Download PDF [1237 KB, uploaded 12 May 2015]   |  

Abstract

The HIV-1 p6 Gag protein contains two late assembly (l-) domains that recruit proteins of the endosomal sorting complex required for transport (ESCRT) pathway to mediate membrane fission between the nascent virion and the cell membrane. It was recently demonstrated that mutation of the highly conserved Ser-40 to Phe (S40F) disturbs CA-SP1 processing, virus morphogenesis, and infectivity. It also causes the formation of filopodia-like structures, while virus release remains unaffected. Here, we show that the mutation S40F, but not the conservative mutation to Asp (S40D) or Asn (S40N), augments membrane association, K48-linked polyubiquitination, entry into the 26S proteasome, and, consequently, enhances MHC-I antigen presentation of Gag derived epitopes. Nuclear magnetic resonance (NMR) structure analyses revealed that the newly introduced Phe-40, together with Tyr-36, causes the formation of a hydrophobic patch at the C-terminal α-helix of p6, providing a molecular rationale for the enhanced membrane association of Gag observed in vitro and in HIV-1 expressing cells. The extended exposure of the S40F mutant to unidentified membrane-resident ubiquitin E3-ligases might trigger the polyubiquitination of Gag. The cumulative data support a previous model of a so far undefined property of p6, which, in addition to MA, acts as membrane targeting domain of Gag. View Full-Text
Keywords: HIV-1; Gag p6; ubiquitination; virus budding; membrane association HIV-1; Gag p6; ubiquitination; virus budding; membrane association
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Hahn, F.; Setz, C.; Friedrich, M.; Rauch, P.; Solbak, S.M.; Frøystein, N.Å.; Henklein, P.; Votteler, J.; Fossen, T.; Schubert, U. Mutation of the Highly Conserved Ser-40 of the HIV-1 p6 Gag Protein to Phe Causes the Formation of a Hydrophobic Patch, Enhances Membrane Association, and Polyubiquitination of Gag. Viruses 2014, 6, 3738-3765.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Viruses EISSN 1999-4915 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top