title: An alternative conformation of the gp41 heptad repeat 1 region coiled coil exists in the human immunodeficiency virus (HIV-1) envelope glycoprotein precursor.
abstract: The human immunodeficiency virus (HIV-1) transmembrane envelope glycoprotein, gp41, which mediates virus-cell fusion, exists in at least three different conformations within the trimeric envelope glycoprotein complex. The structures of the prefusogenic and intermediate states are unknown; structures representing the postfusion state have been solved. In the postfusion conformation, three helical heptad repeat 2 (HR2) regions pack in an antiparallel fashion into the hydrophobic grooves on the surface of a triple-helical coiled coil formed by the heptad repeat 1 (HR1) regions. We studied the prefusogenic conformation of gp41 by mutagenic alteration of membrane-anchored and soluble forms of the HIV-1 envelope glycoproteins. Our results indicate that, in the HIV-1 envelope glycoprotein precursor, the gp41 HR1 region is in a conformation distinct from that of a trimeric coiled coil. Thus, the central gp41 coiled coil is formed during the transition of the HIV-1 envelope glycoproteins from the precursor state to the receptor-bound intermediate.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Claudia C
authors.initials: CC
authors.lastname: Mische
authors.forename: Wen
authors.initials: W
authors.lastname: Yuan
authors.forename: Bettina
authors.initials: B
authors.lastname: Strack
authors.forename: Stewart
authors.initials: S
authors.lastname: Craig
authors.forename: Michael
authors.initials: M
authors.lastname: Farzan
authors.forename: Joseph
authors.initials: J
authors.lastname: Sodroski
mesh_terms: D002460:Cell Line; D014644:Genetic Variation; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000235:genetics; D015497:HIV-1 / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D011487:Protein Conformation; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics; D020836:Protein Structure, Quaternary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D014162:Transfection
chemical_list: D015700:HIV Envelope Protein gp41; D011498:Protein Precursors; D011994:Recombinant Proteins