期刊
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
卷 1818, 期 11, 页码 2521-2528出版社
ELSEVIER
DOI: 10.1016/j.bbamem.2012.06.002
关键词
HIV gp41; MPER-lipid interaction; X-ray scattering; Lytic pore; Membrane curvature
资金
- Spanish Ministerio de Economia y Competitividad, Basque Government
- University of the Basque Country [BIO2011-29792, GIU 06/42]
- Spanish MEU
- National Institutes of Health [R01 AI073892]
- DARPA [W911NF-09-1-378]
- National Science Foundation/Department of Energy [NSF/CHE-0822838]
- U. S. Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-06CH11357]
- Division Of Chemistry
- Direct For Mathematical & Physical Scien [0822838] Funding Source: National Science Foundation
Membrane-activity of the glycoprotein 41 membrane-proximal external region (MPER) is required for HIV-1 membrane fusion. Consequently, its inhibition results in viral neutralization by the antibody 4E10. Previous studies suggested that MPER might act during fusion by locally perturbing the viral membrane, i.e., following a mechanism similar to that proposed for certain antimicrobial peptides. Here, we explore the molecular mechanism of how MPER permeates lipid monolayers containing cholesterol, a main component of the viral envelope, using grazing incidence X-ray diffraction and X-ray reflectivity. Our studies reveal that helical MPER forms lytic pores under conditions not affecting the lateral packing order of lipids. Moreover, we observe an increment of the surface area occupied by MPER helices in cholesterol-enriched membranes, which correlates with an enhancement of the 4E10 epitope accessibility in lipid vesicles. Thus, our data support the view that curvature generation by MPER hydrophobic insertion into the viral membrane is functionally more relevant than lipid packing disruption. (C) 2012 Elsevier B.V. All rights reserved.
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