Purdue University Interdisciplinary Life Sciences Program, West Lafayette, United States.
Department of Biological Sciences,Purdue University, West Lafayette, United States.
Elife. 2021 Nov 9;10:e71683. doi: 10.7554/eLife.71683.
Lactoferrin-binding protein B (LbpB) is a lipoprotein present on the surface of that has been postulated to serve dual functions during pathogenesis in both iron acquisition from lactoferrin (Lf), and in providing protection against the cationic antimicrobial peptide lactoferricin (Lfcn). While previous studies support a dual role for LbpB, exactly how these ligands interact with LbpB has remained unknown. Here, we present the structures of LbpB from and in complex with human holo-Lf, forming a 1:1 complex and confirmed by size-exclusion chromatography small-angle X-ray scattering. LbpB consists of N- and C-lobes with the N-lobe interacting extensively with the C-lobe of Lf. Our structures provide insight into LbpB's preference towards holo-Lf, and our mutagenesis and binding studies show that Lf and Lfcn bind independently. Our studies provide the molecular details for how LbpB serves to capture and preserve Lf in an iron-bound state for delivery to the membrane transporter LbpA for iron piracy, and as an antimicrobial peptide sink to evade host immune defenses.
乳铁蛋白结合蛋白 B（LbpB）是一种脂蛋白，存在于表面，据推测在发病机制中具有双重功能，既能从乳铁蛋白（Lf）中获取铁，又能提供对阳离子抗菌肽乳铁蛋白（Lfcn）的保护。虽然先前的研究支持 LbpB 的双重作用，但这些配体与 LbpB 的相互作用方式仍不清楚。在这里，我们展示了来自 和 的 LbpB 与人源全铁乳铁蛋白（holo-Lf）形成 1:1 复合物的结构，通过大小排阻色谱-小角 X 射线散射得到证实。LbpB 由 N-和 C-结构域组成，N-结构域与 Lf 的 C-结构域广泛相互作用。我们的结构提供了深入了解 LbpB 对全铁乳铁蛋白的偏好的信息，我们的突变和结合研究表明 Lf 和 Lfcn 独立结合。我们的研究提供了分子细节，说明了 LbpB 如何作为一种铁结合状态的乳铁蛋白的捕获和保护者，以便将其递送至膜转运蛋白 LbpA 进行铁掠夺，并作为一种抗菌肽汇逃避宿主免疫防御。
