Assembly of subtype 1 influenza neuraminidase is driven by both the transmembrane and head domains
| Autor: | Johan Nordholm, Diogo V. da Silva, Robert Daniels, Annika Pfeiffer, Ursula Madjo |
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| Rok vydání: | 2012 |
| Předmět: |
Models
Molecular Protein Conformation Protein domain Molecular Conformation Neuraminidase Biochemistry Protein structure Dogs Influenza Human Animals Humans Molecular Biology Glycoproteins biology Chemistry Wild type virus diseases Membrane Proteins Cell Biology Transmembrane protein Protein Structure Tertiary stomatognathic diseases Transmembrane domain Kinetics HEK293 Cells Membrane protein Protein Structure and Folding biology.protein Biophysics human activities Dimerization Homotetramer HeLa Cells Plasmids |
| Zdroj: | The Journal of biological chemistry. 288(1) |
| ISSN: | 1083-351X |
| Popis: | Neuraminidase (NA) is one of the two major influenza surface antigens and the main influenza drug target. Although NA has been well characterized and thought to function as a tetramer, the role of the transmembrane domain (TMD) in promoting proper NA assembly has not been systematically studied. Here, we demonstrate that in the absence of the TMD, NA is synthesized and transported in a predominantly inactive state. Substantial activity was rescued by progressive truncations of the stalk domain, suggesting the TMD contributes to NA maturation by tethering the stalk to the membrane. To analyze how the TMD supports NA assembly, the TMD was examined by itself. The NA TMD formed a homotetramer and efficiently trafficked to the plasma membrane, indicating the TMD and enzymatic head domain drive assembly together through matching oligomeric states. In support of this, an unrelated strong oligomeric TMD rescued almost full NA activity, whereas the weak oligomeric mutant of this TMD restored only half of wild type activity. These data illustrate that a large soluble domain can force assembly with a poorly compatible TMD; however, optimal assembly requires coordinated oligomerization between the TMD and the soluble domain. |
| Databáze: | OpenAIRE |
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