Interactions between HIV-1 gp41 core and detergents and their implications for membrane fusion.
The gp41 envelope protein mediates entry of human immunodeficiency virus type 1 (HIV-1) into the cell by promoting membrane fusion. The crystal structure of a gp41 ectodomain core in its fusion-active state is a six-helix bundle in which a N-terminal trimeric coiled coil is surrounded by three C-terminal outer helices in an antiparallel orientation. Here we demonstrate that the N34(L6)C28 model of the gp41 core is stabilized by interaction with the ionic detergent sodium dodecyl sulfate (SDS) or the nonionic detergent n-octyl-beta-D-glucopyranoside (betaOG). The high resolution x-ray structures of N34(L6)C28 crystallized from two different detergent micellar media reveal a six-helix bundle conformation very similar to that of the molecule in water. Moreover, N34(L6)C28 adopts a highly alpha-helical conformation in lipid vesicles. Taken together, these results suggest that the six-helix bundle of the gp41 core displays substantial affinity for lipid bilayers rather than unfolding in the membrane environment. This characteristic may be important for formation of the fusion-active gp41 core structure and close apposition of the viral and cellular membranes for fusion.
Shu
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Department of Biochemistry, Weill Medical College of Cornell University, New York, New York, 10021, USA.
Ji
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Lu
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D000595:Amino Acid Sequence; D002942:Circular Dichroism; D003461:Crystallography; D003902:Detergents / Q000494:pharmacology; D005960:Glucosides / Q000494:pharmacology; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000378:metabolism*; D015497:HIV-1 / Q000737:chemistry / Q000378:metabolism*; D008561:Membrane Fusion / Q000187:drug effects; D008823:Micelles; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D011994:Recombinant Proteins / Q000378:metabolism; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D013501:Surface-Active Agents / Q000494:pharmacology; D013696:Temperature; D014461:Ultracentrifugation; D014758:Viral Core Proteins / Q000737:chemistry / Q000378:metabolism*
D003902:Detergents; D005960:Glucosides; D015700:HIV Envelope Protein gp41; D008823:Micelles; D011994:Recombinant Proteins; D013501:Surface-Active Agents; D014758:Viral Core Proteins; C018619:octyl-beta-D-glucoside; D012967:Sodium Dodecyl Sulfate