Journal article
Lipid specificity of the immune effector perforin
AW Hodel, JA Rudd-Schmidt, JA Trapani, I Voskoboinik, BW Hoogenboom
Faraday Discussions | ROYAL SOC CHEMISTRY | Published : 2021
DOI: 10.1039/d0fd00043d
Abstract
Perforin is a pore forming protein used by cytotoxic T lymphocytes to remove cancerous or virus-infected cells during the immune response. During the response, the lymphocyte membrane becomes refractory to perforin function by accumulating densely ordered lipid rafts and externalizing negatively charged lipid species. The dense membrane packing lowers the capacity of perforin to bind, and the negatively charged lipids scavenge any residual protein before pore formation. Using atomic force microscopy on model membrane systems, we here provide insight into the molecular basis of perforin lipid specificity. This journal is
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Awarded by UK Research and Innovation
Funding Acknowledgements
We thank Richard Thorogate, Elena Taran, and Tian Zheng for technical support and access to AFM facilities; Peter Andrew and Rana Lonnen for providing PFO; and Sandra Verschoor and Annette Ciccone for expression and purification of perforin and perforin mutants. This work has been funded by an NHMRC Project Grant (1128587), an NHMRC Fellowship (1059126), the BBSRC (BB/J005932/1, BB/J006254/1 and BB/N015487/1); the EPSRC (EP/M028100/1); the Sackler Foundation; and a Swiss National Science Foundation Grant (p2skp3_187634).