Biomolecular Self-Assembly Group, Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, P.O. Box 286, H-1519, Budapest, Hungary.
Biomolecular Self-Assembly Group, Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, P.O. Box 286, H-1519, Budapest, Hungary.
Biochem Biophys Res Commun. 2020 Jun 4;526(3):780-785. doi: 10.1016/j.bbrc.2020.03.162. Epub 2020 Apr 4.
A growing number of evidence shows that human-associated microbiota is an important contributor in health and disease. However, much of the complexity of host-microbiota interaction remains to be elucidated both at cellular and molecular levels. Siderophores are chemically diverse, ferric-specific chelators synthesized and secreted by microbes to secure their iron acquisition. The host defense peptide LL-37 is ubiquitously produced at epithelial surfaces modulating microbial communities and suppressing pathogenic strains. The present work demonstrates that LL-37 binds tightly siderocalin-resistant stealth siderophores which are important contributors to the virulence of several pathogens. As indicated by circular dichroism spectroscopic experiments, addition of aerobactin and rhizoferrin increases the membrane active α-helical conformation of the partially folded peptide. The cationic nature of LL-37 (+6 net charge at pH 7.4) and the multiple carboxylate groups present in siderophores refer to the dominant contribution of electrostatic interactions in the stabilization of peptide-chelator adducts. It is proposed that aside siderocalin proteins, LL-37 may be a complementary, less specific component of the siderophore scavenging repertoire of the innate immune system.
越来越多的证据表明，人类相关的微生物群是健康和疾病的重要贡献者。然而，在细胞和分子水平上，宿主-微生物相互作用的许多复杂性仍有待阐明。铁载体是微生物合成和分泌的化学多样性、三价铁特异性螯合剂，用于确保其铁的获取。宿主防御肽 LL-37 广泛存在于上皮表面，调节微生物群落并抑制致病菌株。本工作表明，LL-37 与耐 siderocalin 的隐形 siderophore 紧密结合，这些隐形 siderophore 是几种病原体毒力的重要贡献者。如圆二色性光谱实验所示，添加 aerobactin 和 rhizoferrin 会增加部分折叠肽的膜活性 α-螺旋构象。LL-37 的阳离子性质（在 pH 7.4 时带 6 个净电荷）和铁载体中存在的多个羧酸盐基团表明静电相互作用在稳定肽-配体加合物中起主要作用。据推测，除了 siderocalin 蛋白外，LL-37 可能是先天免疫系统 siderophore 清除 repertoire 的一种补充、不太特异的成分。
