4Y1S

Structural basis for Ca2+-mediated interaction of the perforin C2 domain with lipid membranes

4Y1S の概要

• エントリーDOI: 10.2210/pdb4y1s/pdb
• 関連するPDBエントリー: 4Y1T
• 分子名称: Perforin-1, CALCIUM ION (3 entities in total)
• 機能のキーワード: perforin, c2 domain, calcium binding, immune system
• 由来する生物種: Mus musculus (house mouse)
• 細胞内の位置: Cytoplasmic granule lumen: P10820
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16515.17

構造登録者

Conroy, P.J.,Yagi, H.,Whisstock, J.C.,Norton, R.S. (登録日: 2015-02-09, 公開日: 2015-09-02, 最終更新日: 2024-11-06)

主引用文献

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

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: 26306037
DOI: 10.1074/jbc.M115.668384

実験手法

X-RAY DIFFRACTION (1.611 Å)