title: Human immunodeficiency virus type 1 envelope glycoprotein oligomerization requires the gp41 amphipathic alpha-helical/leucine zipper-like sequence.
abstract: Human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) oligomerization was investigated by coexpressing wild-type and truncated envelope glycoproteins to determine the minimum sequence required for mutant-wild-type hetero-oligomerization. The gp41 putative amphipathic alpha-helix, Leu-550 to Leu-582, was essential for hetero-oligomer formation. Alanine substitution of 9 of the 10 residues composing the gp41 amphipathic alpha-helix 4-3 hydrophobic repeat sequence was required to inhibit mutant-wild-type hetero-oligomerization and to render the envelope glycoprotein precursor, gp160, monomeric. This indicates that multiple hydrophobic contacts contribute to the stable envelope glycoprotein oligomeric structure. Single alanine substitutions within the hydrophobic repeat sequence did not affect gp160 oligomeric structure but abolished syncytium-forming function. Some mutations also diminished gp160 processing efficiency and the association between gp120 and gp41 in a position-dependent manner. These results indicate that the gp41 amphipathic alpha-helix 4-3 hydrophobic repeat sequence plays a central role in HIV-1 envelope glycoprotein oligomerization and fusion function.
authors.affiliation: St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia. andy_poumbourios.medicine@muwayf.unimelb.edu.au
authors.forename: P
authors.initials: P
authors.lastname: Poumbourios
authors.forename: K A
authors.initials: KA
authors.lastname: Wilson
authors.forename: R J
authors.initials: RJ
authors.lastname: Center
authors.forename: W
authors.initials: W
authors.lastname: El Ahmar
authors.forename: B E
authors.initials: BE
authors.lastname: Kemp
mesh_terms: D000409:Alanine; D000595:Amino Acid Sequence; D019302:HIV Envelope Protein gp160 / Q000502:physiology; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry*; D016350:Leucine Zippers; D008969:Molecular Sequence Data; D016296:Mutagenesis; D013329:Structure-Activity Relationship; D019065:Virus Assembly
chemical_list: D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41; D016056:Immunodominant Epitopes; D000409:Alanine