Defining the interaction of perforin with calcium and the phospholipid membrane

Daouda A K Traore, Amelia J Brennan, Ruby Hong Ping Law, Con Dogovski, Matthew Anthony Perugini, Natalya Lukoyanova, Eleanor Wai Wai Leung, Raymond Stanley Norton, Jamie Lopez, Kylie A Browne, Hideo Yagita, Gordon Lloyd, Annette Ciccone, Sandra Verschoor, Joseph A Trapani, James Whisstock, Ilia Voskoboinik

Research output: Contribution to journalArticleResearchpeer-review

15 Citations (Scopus)


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/perforinlike) domain, indicating that subsequent monomer-monomer interactions at the membrane surface are required for perforin pore formation.
Original languageEnglish
Pages (from-to)323 - 335
Number of pages13
JournalBiochemical Journal
Issue number3
Publication statusPublished - 2013

Cite this