title: Trimerization specificity in HIV-1 gp41: analysis with a GCN4 leucine zipper model.
abstract: The envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) consists of a complex of two noncovalently associated subunits, gp120 and gp41. Formation of gp120/gp41 oligomers is thought to be dependent on a 4-3 hydrophobic (heptad) repeat located in the amino-terminal region of the gp41 molecule. We have investigated the role of this heptad repeat in determining the oligomeric structure of gp41 by introducing its buried core residues into the first (a) and fourth (d) positions of the GCN4 leucine-zipper dimerization domain. The mutant peptides fold into trimeric, helical structures, as shown by circular dichroism and equilibrium sedimentation centrifugation. The 2.4 A resolution crystal structure of one such trimer reveals a parallel three-stranded, alpha-helical coiled coil. Thus, the buried core residues from the gp41 heptad repeat direct trimer formation. We suggest that the conserved amino-terminal heptad repeat within the gp41 ectodomain possesses trimerization specificity.
authors.affiliation: Department of Biochemistry, Weill Medical College of Cornell University, New York 10021, USA.
authors.forename: W
authors.initials: W
authors.lastname: Shu
authors.forename: H
authors.initials: H
authors.lastname: Ji
authors.forename: M
authors.initials: M
authors.lastname: Lu
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D003198:Computer Simulation; D003460:Crystallization; D004268:DNA-Binding Proteins; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics; D015700:HIV Envelope Protein gp41 / Q000737:chemistry*; D015497:HIV-1 / Q000737:chemistry*; D006801:Humans; D016350:Leucine Zippers / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011494:Protein Kinases / Q000737:chemistry* / Q000235:genetics; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D029701:Saccharomyces cerevisiae Proteins
chemical_list: D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D015700:HIV Envelope Protein gp41; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases