1. Defining the interaction of perforin with calcium and the phospholipid membrane
- Author
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Raymond S. Norton, Eleanor W. W. Leung, Annette Ciccone, Matthew A. Perugini, Natalya Lukoyanova, Hideo Yagita, Gordon J. Lloyd, Jamie A. Lopez, Joseph A. Trapani, Daouda A K Traore, James C. Whisstock, Sandra Verschoor, Kylie A. Browne, Con Dogovski, Ruby H. P. Law, Ilia Voskoboinik, and Amelia J. Brennan
- Subjects
Pore Forming Cytotoxic Proteins ,Conformational change ,Biochemistry ,Pore forming protein ,Cell membrane ,Jurkat Cells ,Mice ,medicine ,Animals ,Humans ,Molecular Biology ,Phospholipids ,C2 domain ,Mice, Knockout ,MACPF ,biology ,Cell Membrane ,Cell Biology ,Protein Structure, Tertiary ,Rats ,Cell biology ,medicine.anatomical_structure ,Perforin ,Granzyme ,biology.protein ,Calcium ,K562 Cells ,Complement membrane attack complex - 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.
- Published
- 2013
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