Intramolecular backfolding of the carboxyl-terminal end of MxA protein is a prerequisite for its oligomerization
| Autor: | Jovan Pavlovic, Hans Peter Hefti, Claudio Di Paolo, Heinrich Landis, Marina L. Meli |
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| Přispěvatelé: | University of Zurich, Pavlovic, J |
| Rok vydání: | 1999 |
| Předmět: |
10028 Institute of Medical Virology
Myxovirus Resistance Proteins Protein Folding 1303 Biochemistry Polymers Mutant 610 Medicine & health GTPase Biology Biochemistry Protein Structure Secondary 1307 Cell Biology Mice Interferon GTP-Binding Proteins Leucine 1312 Molecular Biology medicine Moiety Animals Humans Molecular Biology chemistry.chemical_classification Intermolecular force RNA Proteins Cell Biology 3T3 Cells Amino acid Phenotype chemistry Intramolecular force Biophysics 570 Life sciences biology Peptides Oligopeptides medicine.drug |
| Zdroj: | The Journal of biological chemistry. 274(45) |
| ISSN: | 0021-9258 |
| Popis: | Mx proteins are large GTPases, which play a pivotal role in the interferon type I-mediated response against viral infections. The human MxA inhibits the replication of several RNA viruses and is organized in oligomeric structures. Using two different experimental approaches, the mammalian two-hybrid system and an interaction dependent nuclear translocation approach, three domains in the carboxyl-terminal moiety were identified that are involved in the oligomerization of MxA. The first consists of a carboxyl-terminal amphipathic helix (LZ1), which binds to a more proximal part of the same molecule. This intramolecular backfolding is a prerequisite for the formation of an intermolecular complex. This intermolecular interaction is mediated by two domains, a poorly defined region generated by the intramolecular interaction and a domain located between amino acids 363 and 415. Co-expression of wild-type MxA with various mutant fragments thereof revealed that the presence of the carboxyl-terminal region comprising the amphipathic helices LZ1 and LZ2 is necessary and sufficient to exert a dominant negative effect. This finding suggests that the functional interference of the carboxyl-terminal region is due to competition for binding of an as yet unidentified cellular or viral target molecules. |
| Databáze: | OpenAIRE |
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