Determinants of CD81 dimerization and interaction with hepatitis C virus glycoprotein E2
| Autor: | Kirilee A. Wilson, Heidi E. Drummer, Pantelis Poumbourios |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
viruses
Molecular Sequence Data Biophysics Molecular Conformation chemical and pharmacologic phenomena Plasma protein binding CHO Cells Biology Kidney Biochemistry Cell Line Tetraspanin 28 Mice Structure-Activity Relationship Cricetulus Tetraspanin Viral Envelope Proteins Antigens CD Cricetinae Animals Humans Amino Acid Sequence Binding site Amino Acids Molecular Biology Peptide sequence chemistry.chemical_classification Binding Sites Kidney metabolism Cell Biology biochemical phenomena metabolism and nutrition Molecular biology biological factors Recombinant Proteins Molecular Weight chemistry Mutagenesis Site-Directed NIH 3T3 Cells Salt bridge Glycoprotein Dimerization CD81 Protein Binding |
| Zdroj: | Biochemical and biophysical research communications. 328(1) |
| ISSN: | 0006-291X |
| Popis: | The tetraspanin CD81 plays an essential role in diverse cellular processes. CD81 also acts as an entry receptor for HCV through an interaction between the large extracellular loop (LEL) of CD81 and HCV glycoprotein E2. The E2-CD81 interaction also results in immunomodulatory effects in vitro. In this study, we examined the relationship between the dimeric crystal structure of the CD81 LEL and intact CD81. Using random mutagenesis, amino acids were identified that abolished dimerization of recombinant LEL in regions that were important for intermonomer contacts (F150S and V146E), salt bridge formation (K124T), and intramonomer disulfide bonding (T166I, C157S, and C190R). Two monomeric LEL mutants retained the ability to bind E2, K124T, and V146E, whereas F150S, T166I, C157S, and C190R did not. Introduction of K124T, V146E, and F150S mutations in full-length CD81 did not affect its oligomerization and the effects on E2 binding were less severe than for isolated LEL. These results suggest that the LEL has a more robust structure in the intact tetraspanin with regions outside the LEL contributing to CD81 dimerization. |
| Databáze: | OpenAIRE |
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