Dr. Robert Daniels, Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University
Monday 10th March, 4.00 p.m., Marlowe Lecture Theatre 1
Transmembrane domains (TMDs) from single-spanning membrane proteins are commonly viewed as hydrophobic membrane anchors for functional domains. Influenza neuraminidase (NA) exemplifies this concept as it retains enzymatic function upon proteolytic release from the membrane. However, we recently showed that the TMD is required for the proper folding of the NA head domain (1), and that the NA TMDs in human H1N1 viruses have become increasingly less hydrophobic, which has altered their assembly by enhancing the TMD association (2). These results suggested that the TMD from NA is changing to maintain compatibility with the distal enzymatic head domain. The seminar will cover our current work on the investigation of this relationship where we analyzed influenza A viruses encoding NA chimeras where the amphipathic TMDs from an old and modern NA (N1) were exchanged, or replaced by an engineered hydrophobic TMD (3). The results from this work provide a likely explanation for why the NA TMDs became more polar, show how modifying the intrinsic TMD folding properties can adapt a distal domain to its environment, and how the virus exploits the co-translation insertion process to support the membrane insertion of these marginally hydrophobic TMDs.
- da Silva, D. V., Nordholm, J., Madjo, U., Pfeiffer, A., and Daniels, R. (2013) Assembly of subtype 1 influenza neuraminidase is driven by both the transmembrane and head domains. J Biol Chem 288, 644-653
- Nordholm, J., da Silva, D. V., Damjanovic, J., Dou, D., and Daniels, R. (2013) Polar residues and their positional context dictate the transmembrane domain interactions of influenza a neuraminidases. J Biol Chem 288, 10652-10660
- da Silva, D. V., Nordholm, J., Dou, D., and Daniels, R. (2014) Temperature adaptation of influenza A viruses through the NA transmembrane domain. Submitted