Ellis-Guardiola Ken, Mahoney Brendan J, Clubb Robert T
Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, United States.
UCLA-DOE Institute for Genomics and Proteomics, University of California, Los Angeles, Los Angeles, CA, United States.
Front Microbiol. 2021 Jan 6;11:607679. doi: 10.3389/fmicb.2020.607679. eCollection 2020.
Iron is an important micronutrient that is required by bacteria to proliferate and to cause disease. Many bacterial pathogens forage iron from human hemoglobin (Hb) during infections, which contains this metal within heme (iron-protoporphyrin IX). Several clinically important pathogenic species within the Firmicutes phylum scavenge heme using surface-displayed or secreted NEAr Transporter (NEAT) domains. In this review, we discuss how these versatile proteins function in the Iron-regulated surface determinant system that scavenges heme-iron from Hb. NEAT domains function as either Hb receptors or as heme-binding chaperones. studies have shown that heme-binding NEAT domains can rapidly exchange heme amongst one another via transiently forming transfer complexes, leading to the interesting hypothesis that they may form a protein-wire within the peptidoglycan layer through which heme flows from the microbial surface to the membrane. In Hb receptors, recent studies have revealed how dedicated heme- and Hb-binding NEAT domains function synergistically to extract Hb's heme molecules, and how receptor binding to the Hb-haptoglobin complex may block its clearance by macrophages, prolonging microbial access to Hb's iron. The functions of NEAT domains in other Gram-positive bacteria are also reviewed.
铁是一种重要的微量营养素，细菌增殖和致病都需要它。许多细菌病原体在感染期间从人类血红蛋白（Hb）中获取铁，血红蛋白在血红素（铁原卟啉IX）中含有这种金属。厚壁菌门中的几种临床上重要的致病物种利用表面展示或分泌的近转运体（NEAT）结构域来清除血红素。在这篇综述中，我们讨论了这些多功能蛋白在铁调节表面决定簇系统中如何发挥作用，该系统从血红蛋白中清除血红素铁。NEAT结构域既可以作为血红蛋白受体，也可以作为血红素结合伴侣发挥作用。研究表明，结合血红素的NEAT结构域可以通过短暂形成转移复合物在彼此之间快速交换血红素，从而引出了一个有趣的假设，即它们可能在肽聚糖层内形成一条蛋白质线，血红素通过这条线从微生物表面流向细胞膜。在血红蛋白受体方面，最近的研究揭示了专门结合血红素和血红蛋白的NEAT结构域如何协同作用以提取血红蛋白中的血红素分子，以及受体与血红蛋白-触珠蛋白复合物的结合如何阻止巨噬细胞对其清除，从而延长微生物获取血红蛋白中铁的时间。本文还综述了NEAT结构域在其他革兰氏阳性菌中的功能。
