5W1F

Crystal structure of Ni(II)- and Ca(II)-bound human calprotectin

5W1F の概要

• エントリーDOI: 10.2210/pdb5w1f/pdb
• 分子名称: Protein S100-A8, Protein S100-A9, SODIUM ION, ... (6 entities in total)
• 機能のキーワード: calprotectin, innate immunity, metal sequestration, nickel, calcium, s100 protein, metal binding protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 97232.55

構造登録者

Nakashige, T.G.,Drennan, C.L.,Nolan, E.M. (登録日: 2017-06-03, 公開日: 2017-06-14, 最終更新日: 2023-10-04)

主引用文献

Nakashige, T.G.,Zygiel, E.M.,Drennan, C.L.,Nolan, E.M.
Nickel Sequestration by the Host-Defense Protein Human Calprotectin.
J. Am. Chem. Soc., 139:8828-8836, 2017

PubMed Abstract: The human innate immune protein calprotectin (CP, S100A8/S100A9 oligomer, calgranulin A/calgranulin B oligomer, MRP-8/MRP-14 oligomer) chelates a number of first-row transition metals, including Mn(II), Fe(II), and Zn(II), and can withhold these essential nutrients from microbes. Here we elucidate the Ni(II) coordination chemistry of human CP. We present a 2.6-Å crystal structure of Ni(II)- and Ca(II)-bound CP, which reveals that CP binds Ni(II) ions at both its transition-metal-binding sites: the HisAsp motif (site 1) and the His motif (site 2). Further biochemical studies establish that coordination of Ni(II) at the hexahistidine site is thermodynamically preferred over Zn(II). We also demonstrate that CP can sequester Ni(II) from two human pathogens, Staphylococcus aureus and Klebsiella pneumoniae, that utilize this metal nutrient during infection, and inhibit the activity of the Ni(II)-dependent enzyme urease in bacterial cultures. In total, our findings expand the biological coordination chemistry of Ni(II)-chelating proteins in nature and provide a foundation for evaluating putative roles of CP in Ni(II) homeostasis at the host-microbe interface and beyond.

PubMed: 28573847
DOI: 10.1021/jacs.7b01212

実験手法

X-RAY DIFFRACTION (2.6 Å)