Analysis of Perforin Assembly by Quartz Crystal Microbalance Reveals a Role for Cholesterol and Calcium-independent Membrane Binding
Sarah E Stewart, Catherina H Bird, Rico F Tabor, Michael E D'Angelo, Stefania Piantavigna, James C Whisstock, Joseph A Trapani, Lisandra L Martin, Phillip I Bird
Journal of Biological Chemistry | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | Published : 2015
Perforin is an essential component in the cytotoxic lymphocyte-mediated cell death pathway. The traditional view holds that perforin monomers assemble into pores in the target cell membrane via a calcium-dependent process and facilitate translocation of cytotoxic proteases into the cytoplasm to induce apoptosis. Although many studies have examined the structure and role of perforin, the mechanics of pore assembly and granzyme delivery remain unclear. Here we have employed quartz crystal microbalance with dissipation monitoring (QCM-D) to investigate binding and assembly of perforin on lipid membranes, and show that perforin monomers bind to the membrane in a cooperative manner. We also found..View full abstract
This work was supported by grants from the National Health and Medical Research Council (Australia) (to P. I. B. and J. C. W.) and by grants from the Australian Research Council (to L. L. M R. F. T., and J. C. W.). The authors declare that they have no conflicts of interest with the contents of this article.