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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Da Silva, Diogo V. Pfeiffer, Annika Daniels, Robert Madjo, Ursula Nordholm, Johan |
| Description | Author Affiliation: da Silva DV ( Department of Biochemistry and Biophysics, Center for Biomembrane Research, Stockholm University, SE-106 91 Stockholm, Sweden.) |
| Abstract | 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. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 1 |
| Volume Number | 288 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2013-01-04 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Influenza, Human Enzymology Neuraminidase Chemistry Animals Dimerization Glycoproteins HEK293 Cells HeLa Cells Kinetics Membrane Proteins Models, Molecular Molecular Conformation Metabolism Plasmids Protein Conformation Protein Structure, Tertiary Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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