4Y1S
Structural basis for Ca2+-mediated interaction of the perforin C2 domain with lipid membranes
Summary for 4Y1S
| Entry DOI | 10.2210/pdb4y1s/pdb |
| Related | 4Y1T |
| Descriptor | Perforin-1, CALCIUM ION (3 entities in total) |
| Functional Keywords | perforin, c2 domain, calcium binding, immune system |
| Biological source | Mus musculus (house mouse) |
| Cellular location | Cytoplasmic granule lumen: P10820 |
| Total number of polymer chains | 1 |
| Total formula weight | 16515.17 |
| Authors | Conroy, P.J.,Yagi, H.,Whisstock, J.C.,Norton, R.S. (deposition date: 2015-02-09, release date: 2015-09-02, Last modification date: 2024-11-06) |
| Primary citation | Yagi, H.,Conroy, P.J.,Leung, E.W.,Law, R.H.,Trapani, J.A.,Voskoboinik, I.,Whisstock, J.C.,Norton, R.S. Structural Basis for Ca2+-mediated Interaction of the Perforin C2 Domain with Lipid Membranes. J.Biol.Chem., 290:25213-25226, 2015 Cited by PubMed 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 binding. We have also determined the affinities of several of these binding sites and have shown that this interaction causes a significant structural rearrangement in CBR1. Thus, it is proposed that Ca(2+) binding at the weakest affinity site triggers changes in the C2 domain that facilitate its interaction with lipid membranes. PubMed: 26306037DOI: 10.1074/jbc.M115.668384 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.611 Å) |
Structure validation
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