Propensity for a Leucine Zipper-Like Domain of Human Immunodeficiency Virus Type 1 gp41 to Form Oligomers Correlates with a Role in Virus-Induced Fusion Rather than Assembly of the Glycoprotein Complex

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 91; no. 26; pp. 12676 - 12680
• Main Authors: Wild, Carl, Dubay, John W., Greenwell, Teresa, Baird, Teaster, Oas, Terrence G., McDanal, Charlene, Hunter, Eric, Matthews, Thomas
• Format: Journal Article
• Language: English
• Published: United States National Academy of the Sciences of the United States of America 20.12.1994; National Acad Sciences; National Academy of Sciences
• Subjects: Amino Acid Sequence; Amino acids; Biochemistry; Cell Fusion; Cell lines; Circular Dichroism; COS cells; env genes; Glycoproteins; HeLa Cells; HIV; HIV 1; HIV Envelope Protein gp41 - chemistry; HIV-1 - growth & development; Human immunodeficiency virus; human immunodeficiency virus 1; Humans; In Vitro Techniques; Infections; Leucine Zippers; Molecular Sequence Data; Mutagenesis, Site-Directed; Peptides - chemistry; Protein Binding; Structure-Activity Relationship; Transmembrane proteins; Viral Fusion Proteins - chemistry; Viral morphology; Virus Replication; Viruses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.26.12676

For a number of viruses, oligomerization is a critical component of envelope processing and surface expression. Previously, we reported that a synthetic peptide (DP-107) corresponding to the putative leucine zipper region (aa 553-590) of the transmembrane protein (gp41) of human immunodeficiency virus type 1 (HIV-1) exhibited α-helical secondary structure and self-associated as a coiled coil. In view of the tendency of this type of structure to mediate protein association, we speculated that this region of gp41 might play a role in HIV-1 envelope oligomerization. However, later it was shown that mutations which should disrupt the structural elements of this region of gp41 did not affect envelope processing, transport, or surface expression (assembly oligomerization). In this report we compare the effects of amino acid substitutions within this coiled-coil region on structure and function of both viral envelope proteins and the corresponding synthetic peptides. Our results establish a correlation between the destabilizing effects of amino acid substitutions on coiled-coil structure in the peptide model and phenotype of virus entry. These biological and physical biochemical studies do not support a role for the coiled-coil structure in mediating the assembly oligomerization of HIV-1 envelope but do imply that this region of gp41 plays a key role in the sequence of events associated with viral entry. We propose a functional role for the coiled-coil domain of HIV-1 gp41.