Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Biometals. 2023 Aug;36(4):817-828. doi: 10.1007/s10534-023-00493-x. Epub 2023 Feb 24.
Human calprotectin (CP, S100A8/S100A9 oligomer) is an abundant neutrophil protein that contributes to innate immunity by sequestering nutrient metal ions in the extracellular space. This process starves invading microbial pathogens of essential metal nutrients, which can inhibit growth and colonization. Over the past decade, fundamental and clinical studies have revealed that the S100A8 and S100A9 subunits of CP exhibit a variety of post-translational modifications (PTMs). This review summarizes PTMs on the CP subunits that have been detected and highlights two recent studies that evaluated the structural and functional consequences of methionine and cysteine oxidation on CP. Collectively, these investigations indicate that the molecular speciation of extracellular CP is complex and composed of multiple proteoforms. Moreover, PTMs may impact biological function and the lifetime of the protein. It is therefore important that post-translationally modified CP species receive consideration and integration into the current working model for how CP functions in nutritional immunity.
人钙卫蛋白（CP，S100A8/S100A9 寡聚物）是一种丰富的中性粒细胞蛋白，通过在细胞外空间隔离营养金属离子来促进先天免疫。这一过程使入侵的微生物病原体无法获得必需的金属营养物质，从而抑制其生长和定植。在过去的十年中，基础和临床研究揭示了 CP 的 S100A8 和 S100A9 亚基表现出多种翻译后修饰（PTM）。这篇综述总结了已检测到的 CP 亚基上的 PTM，并强调了最近两项评估 CP 上蛋氨酸和半胱氨酸氧化对其结构和功能影响的研究。总的来说，这些研究表明细胞外 CP 的分子形态复杂，由多种蛋白形式组成。此外，PTM 可能影响生物功能和蛋白质的寿命。因此，重要的是要考虑到翻译后修饰的 CP 物种，并将其纳入 CP 在营养免疫中发挥作用的现行工作模型。
