6ZDY

Crystal structure of WT murine S100A9 bound to calcium and zinc

6ZDY の概要

• エントリーDOI: 10.2210/pdb6zdy/pdb
• 分子名称: Protein S100-A9, CALCIUM ION, ZINC ION, ... (5 entities in total)
• 機能のキーワード: calcium-binding protein, homodimer, metal binding protein
• 由来する生物種: Mus musculus (House mouse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 13507.09

構造登録者

Yatime, L. (登録日: 2020-06-15, 公開日: 2021-01-13, 最終更新日: 2024-10-16)

主引用文献

Signor, L.,Paris, T.,Mas, C.,Picard, A.,Lutfalla, G.,Boeri Erba, E.,Yatime, L.
Divalent cations influence the dimerization mode of murine S100A9 protein by modulating its disulfide bond pattern.
J.Struct.Biol., 213:107689-107689, 2020

PubMed Abstract: S100A9, with its congener S100A8, belongs to the S100 family of calcium-binding proteins found exclusively in vertebrates. These two proteins are major constituents of neutrophils. In response to a pathological condition, they can be released extracellularly and become alarmins that induce both pro- and anti-inflammatory signals, through specific cell surface receptors. They also act as antimicrobial agents, mainly as a S100A8/A9 heterocomplex, through metal sequestration. The mechanisms whereby divalent cations modulate the extracellular functions of S100A8 and S100A9 are still unclear. Importantly, it has been proposed that these ions may affect both the ternary and quaternary structure of these proteins, thereby influencing their physiological properties. In the present study, we report the crystal structures of WT and C80A murine S100A9 (mS100A9), determined at 1.45 and 2.35 Å resolution, respectively, in the presence of calcium and zinc. These structures reveal a canonical homodimeric form for the protein. They also unravel an intramolecular disulfide bridge that stabilizes the C-terminal tail in a rigid conformation, thus shaping a second Zn-binding site per S100A9 protomer. In solution, mS100A9 apparently binds only two zinc ions per homodimer, with an affinity in the micromolar range, and aggregates in the presence of excess zinc. Using mass spectrometry, we demonstrate that mS100A9 can form both non-covalent and covalent homodimers with distinct disulfide bond patterns. Interestingly, calcium and zinc seem to affect differentially the relative proportion of these forms. We discuss how the metal-dependent interconversion between mS100A9 homodimers may explain the versatility of physiological functions attributed to the protein.

PubMed: 33359632
DOI: 10.1016/j.jsb.2020.107689

実験手法

X-RAY DIFFRACTION (1.45 Å)