Structural Basis for Ca2+-mediated Interaction of the Perforin C2 Domain with Lipid Membranes.

ABSTRACT: Natural killer cells and cytotoxic T-lymphocytes deploy perforin and granzymes to kill infected host cells. Perforin, secreted by immune cells, binds target membranes to form pores that deliver pro-apoptotic granzymes into the target cell. A crucial first step in this process is interaction of its C2 domain with target cell membranes, which is a calcium-dependent event. Some aspects of this process are understood, but many molecular details remain unclear. To address this, we investigated the mechanism of Ca(2+) and lipid binding to the C2 domain by NMR spectroscopy and x-ray crystallography. Calcium titrations, together with dodecylphosphocholine micelle experiments, confirmed that multiple Ca(2+) ions bind within the calcium-binding regions, activating perforin with respect to membrane b

SUBMITTER: Yagi H 

PROVIDER: S-EPMC4646173 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature