Functional Interaction between Paramyxovirus Fusion and Attachment Proteins
| Autor: | Tanja Paal, Laura K. White, Andrew Prussia, Richard K. Plemper, James P. Snyder, Jin K. Lee |
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| Rok vydání: | 2008 |
| Předmět: |
Models
Molecular Paramyxoviridae Surface Properties Recombinant Fusion Proteins Molecular Sequence Data Mutant Plasma protein binding Biochemistry Measles virus Dogs Cricetinae Chlorocebus aethiops Animals Paramyxovirinae Amino Acid Sequence Distemper Virus Canine Vero Cells Molecular Biology Peptide sequence chemistry.chemical_classification biology Cell Biology biology.organism_classification Virology Molecular biology Membrane Transport Structure Function and Biogenesis Membrane protein chemistry Mutation Glycoprotein Viral Fusion Proteins Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 283:16561-16572 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m801018200 |
| Popis: | Paramyxovirinae envelope glycoproteins constitute a premier model to dissect how specific and dynamic interactions in multisubunit membrane protein complexes can control deep-seated conformational rearrangements. However, individual residues that determine reciprocal specificity of the viral attachment and fusion (F) proteins have not been identified. We have developed an assay based on a pair of canine distemper virus (CDV) F proteins (strains Onderstepoort (ODP) and Lederle) that share ∼95% identity but differ in their ability to form functional complexes with the measles virus (MV) attachment protein (H). Characterization of CDV F chimeras and mutagenesis reveals four residues in CDV F-ODP (positions 164, 219, 233, and 317) required for productive interaction with MV H. Mutating these residues to the Lederle type disrupts triggering of F-ODP by MV H without affecting functionality when co-expressed with CDV H. Co-immunoprecipitation shows a stronger physical interaction of F-ODP than F-Lederle with MV H. Mutagenesis of MV F highlights the MV residues homologous to CDV F residues 233 and 317 as determinants for physical glycoprotein interaction and fusion activity under homotypic conditions. In assay reversal, the introduction of sections of the CDV H stalk into MV H shows a five-residue fragment (residues 110–114) to mediate specificity for CDV F-Lederle. All of the MV H stalk chimeras are surface-expressed, show hemadsorption activity, and trigger MV F. Combining the five-residue H chimera with the CDV F-ODP quadruple mutant partially restores activity, indicating that the residues identified in either glycoprotein contribute interdependently to the formation of functional complexes. Their localization in structural models of F and H suggests that placement in particular of F residue 233 in close proximity to the 110–114 region of H is structurally conceivable. |
| Databáze: | OpenAIRE |
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