Traore, DA.K. and Brennan, A.J. and Law, R.H. P. and Dogovski, C. and Perugini, M.A. and Lukoyanova, Natalya and Leung, E.W.W. and Norton, R.S. and Lopez, J.A. and Browne, K.A. and Yagita, H. and Lloyd, G.J. and Ciccone, A. and Verschoor, S. and Trapani, J.A. and Whisstock, J.C. and Voskoboinik, I. (2013) Defining the interaction of perforin with calcium and the phospholipid membrane. Biochemical Journal 456 (3), pp. 323-335. ISSN 0264-6021.
Abstract
Following its secretion from cytotoxic lymphocytes into the immune synapse, perforin binds to target cell membranes through its Ca2+-dependent C2 domain. Membrane-bound perforin then forms pores that allow passage of pro-apoptopic granzymes into the target cell. In the present study, structural and biochemical studies reveal that Ca2+ binding triggers a conformational change in the C2 domain that permits four key hydrophobic residues to interact with the plasma membrane. However, in contrast with previous suggestions, these movements and membrane binding do not trigger irreversible conformational changes in the pore-forming MACPF (membrane attack complex/perforin-like) domain, indicating that subsequent monomer–monomer interactions at the membrane surface are required for perforin pore formation.
Metadata
| Item Type: | Article |
|---|---|
| Keyword(s) / Subject(s): | apoptosis, C2 domain, cytotoxic lymphocyte, perforin, pore-forming protein |
| School: | Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences |
| Depositing User: | Administrator |
| Date Deposited: | 09 Dec 2013 16:16 |
| Last Modified: | 02 Aug 2023 17:08 |
| URI: | https://eprints.bbk.ac.uk/id/eprint/8804 |
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