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
Autor: | Terrence G. Oas, Eric Hunter, John W. Dubay, Charlene McDanal, Carl T. Wild, Teresa Greenwell, Teaster Baird, Tom Matthews |
---|---|
Rok vydání: | 1994 |
Předmět: |
Leucine zipper
viruses Molecular Sequence Data Biology In Vitro Techniques Gp41 Virus Replication Cell Fusion Structure-Activity Relationship Viral envelope Viral entry Glycoprotein complex Humans Amino Acid Sequence Peptide sequence Protein secondary structure Coiled coil Leucine Zippers Multidisciplinary Circular Dichroism HIV Envelope Protein gp41 Cell biology Biochemistry HIV-1 Mutagenesis Site-Directed Peptides Viral Fusion Proteins HeLa Cells Protein Binding Research Article |
Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 91(26) |
ISSN: | 0027-8424 |
Popis: | 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 alpha-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. |
Databáze: | OpenAIRE |
Externí odkaz: |