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

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/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
Volume456
Issue number3
DOIs
Publication statusPublished - 2013

Cite this

Traore, D. A. K., Brennan, A. J., Law, R. H. P., Dogovski, C., Perugini, M. A., Lukoyanova, N., ... Voskoboinik, I. (2013). Defining the interaction of perforin with calcium and the phospholipid membrane. Biochemical Journal, 456(3), 323 - 335. https://doi.org/10.1042/BJ20130999
Traore, Daouda A K ; Brennan, Amelia J ; Law, Ruby Hong Ping ; Dogovski, Con ; Perugini, Matthew Anthony ; Lukoyanova, Natalya ; Leung, Eleanor Wai Wai ; Norton, Raymond Stanley ; Lopez, Jamie ; Browne, Kylie A ; Yagita, Hideo ; Lloyd, Gordon ; Ciccone, Annette ; Verschoor, Sandra ; Trapani, Joseph A ; Whisstock, James ; Voskoboinik, Ilia. / Defining the interaction of perforin with calcium and the phospholipid membrane. In: Biochemical Journal. 2013 ; Vol. 456, No. 3. pp. 323 - 335.
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title = "Defining the interaction of perforin with calcium and the phospholipid membrane",
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/perforinlike) domain, indicating that subsequent monomer-monomer interactions at the membrane surface are required for perforin pore formation.",
author = "Traore, {Daouda A K} and Brennan, {Amelia J} and Law, {Ruby Hong Ping} and Con Dogovski and Perugini, {Matthew Anthony} and Natalya Lukoyanova and Leung, {Eleanor Wai Wai} and Norton, {Raymond Stanley} and Jamie Lopez and Browne, {Kylie A} and Hideo Yagita and Gordon Lloyd and Annette Ciccone and Sandra Verschoor and Trapani, {Joseph A} and James Whisstock and Ilia Voskoboinik",
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doi = "10.1042/BJ20130999",
language = "English",
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journal = "Biochemical Journal",
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Traore, DAK, Brennan, AJ, Law, RHP, Dogovski, C, Perugini, MA, Lukoyanova, N, Leung, EWW, Norton, RS, Lopez, J, Browne, KA, Yagita, H, Lloyd, G, Ciccone, A, Verschoor, S, Trapani, JA, Whisstock, J & Voskoboinik, I 2013, 'Defining the interaction of perforin with calcium and the phospholipid membrane' Biochemical Journal, vol. 456, no. 3, pp. 323 - 335. https://doi.org/10.1042/BJ20130999

Defining the interaction of perforin with calcium and the phospholipid membrane. / Traore, Daouda A K; Brennan, Amelia J; Law, Ruby Hong Ping; Dogovski, Con; Perugini, Matthew Anthony; Lukoyanova, Natalya; Leung, Eleanor Wai Wai; Norton, Raymond Stanley; Lopez, Jamie; Browne, Kylie A; Yagita, Hideo; Lloyd, Gordon; Ciccone, Annette; Verschoor, Sandra; Trapani, Joseph A; Whisstock, James; Voskoboinik, Ilia.

In: Biochemical Journal, Vol. 456, No. 3, 2013, p. 323 - 335.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Defining the interaction of perforin with calcium and the phospholipid membrane

AU - Traore, Daouda A K

AU - Brennan, Amelia J

AU - Law, Ruby Hong Ping

AU - Dogovski, Con

AU - Perugini, Matthew Anthony

AU - Lukoyanova, Natalya

AU - Leung, Eleanor Wai Wai

AU - Norton, Raymond Stanley

AU - Lopez, Jamie

AU - Browne, Kylie A

AU - Yagita, Hideo

AU - Lloyd, Gordon

AU - Ciccone, Annette

AU - Verschoor, Sandra

AU - Trapani, Joseph A

AU - Whisstock, James

AU - Voskoboinik, Ilia

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Y1 - 2013

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AB - 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.

UR - http://www.ncbi.nlm.nih.gov/pubmed/24070258

U2 - 10.1042/BJ20130999

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JF - Biochemical Journal

SN - 0264-6021

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