Format

Send to

Choose Destination
Biophys J. 2014 Feb 4;106(3):577-85. doi: 10.1016/j.bpj.2013.12.019.

Coarse-grained simulations of the HIV-1 matrix protein anchoring: revisiting its assembly on membrane domains.

Author information

1
Institut des Biomolécules Max Mousseron (IBMM), CNRS UMR5247, Université Montpellier 1, Université Montpellier 2, Faculté de Pharmacie, Montpellier cedex 05, France.
2
Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé (CPBS) CNRS-UMR 5236, Université Montpellier 1 - Université Montpellier 2, Montpellier Cedex 5, France.
3
Dynamique des Structures et Interactions des Macromolécules Biologiques INTS, INSERM UMR-S665, Université Paris Diderot, Alexandre Cabanel, Paris.
4
Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé (CPBS) CNRS-UMR 5236, Université Montpellier 1 - Université Montpellier 2, Montpellier Cedex 5, France. Electronic address: cyril.favard@cpbs.cnrs.fr.
5
Institut des Biomolécules Max Mousseron (IBMM), CNRS UMR5247, Université Montpellier 1, Université Montpellier 2, Faculté de Pharmacie, Montpellier cedex 05, France. Electronic address: nicolas.floquet@univ-montp1.fr.

Abstract

In the accepted model for human immunodeficiency virus preassembly in infected host cells, the anchoring to the intracellular leaflet of the membrane of the matrix domain (MA) that lies at the N-terminus of the viral Gag protein precursor appears to be one of the crucial steps for particle assembly. In this study, we simulated the membrane anchoring of human immunodeficiency virus-1 myristoylated MA protein using a coarse-grained representation of both the protein and the membrane. Our calculations first suggest that the myristoyl group could spontaneously release from its initial hydrophobic pocket before MA protein interacts with the lipid membrane. All-atom simulations confirmed this possibility with a related energy cost estimated to be ~5 kcal.mol(-1). The phosphatidylinositol (4,5) bisphosphate (PI(4,5)P2) head binds preferentially to the MA highly basic region as described in available NMR data, but interestingly without flipping of its 2' acyl chain into the MA protein. Moreover, MA was able to confine PI(4,5)P2 lipids all around its molecular surface after having found a stable orientation at the membrane surface. Our results suggest that this orientation is dependent on Myr anchoring and that this confinement induces a lateral segregation of PI(4,5)P2 in domains. This is consistent with a PI(4,5)P2 enrichment of the virus envelope as compared to the host cell membrane.

PMID:
24507598
PMCID:
PMC3944987
DOI:
10.1016/j.bpj.2013.12.019
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center