Center for Infectious & Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas, United States of America.
PLoS Pathog. 2010 Jan 15;6(1):e1000726. doi: 10.1371/journal.ppat.1000726.
Gram-positive bacteria contain a family of surface proteins that are covalently anchored to the cell wall of the organism. These cell-wall anchored (CWA) proteins appear to play key roles in the interactions between pathogenic organisms and the host. A subfamily of the CWA has a common structural organization with multiple domains adopting characteristic IgG-like folds. The identified microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) belong to this subfamily, as does SdrC from S. aureus. However, an interactive host ligand for the putative MSCRAMM SdrC was not previously identified. We have screened a phage display peptide library and identified a peptide sequence found in beta-neurexin that binds SdrC. A synthetic peptide corresponding to the identified sequence as well as a recombinant form of the beta-neurexin 1 exodomain binds SdrC with high affinity and specificity. Furthermore, expression of SdrC on bacteria greatly enhances microbial adherence to cultured mammalian cells expressing beta-neurexin on their surface. Taken together, our experimental results demonstrate that beta-neurexin is a ligand for SdrC. This interaction involves a specific sequence located in the N-terminal region of the mammalian protein and the N(2)N(3) domain of the MSCRAMM. The fact that these two proteins interact when expressed on the appropriate cells demonstrates the functionality of the interaction. Possible implications of this interaction are discussed.
革兰氏阳性菌含有一组通过共价键锚定在生物体细胞壁上的表面蛋白。这些细胞壁锚定（CWA）蛋白似乎在病原生物与宿主之间的相互作用中发挥关键作用。CWA 的一个亚家族具有共同的结构组织，多个结构域采用特征性的 IgG 样折叠。已鉴定的微生物表面识别黏附基质分子的成分（MSCRAMM）属于这个亚家族，金黄色葡萄球菌的 SdrC 也是如此。然而，以前没有确定 SdrC 的假定 MSCRAMM 的互作宿主配体。我们已经筛选了噬菌体展示肽文库，并鉴定出与 SdrC 结合的β-神经连接蛋白中的肽序列。与鉴定出的序列相对应的合成肽以及β-神经连接蛋白 1 外显子的重组形式与 SdrC 具有高亲和力和特异性结合。此外，细菌表面表达 SdrC 大大增强了微生物对表面表达β-神经连接蛋白的培养哺乳动物细胞的黏附。总之，我们的实验结果表明β-神经连接蛋白是 SdrC 的配体。这种相互作用涉及位于哺乳动物蛋白 N 端区域和 MSCRAMM 的 N(2)N(3)结构域的特定序列。当在适当的细胞上表达这两种蛋白时相互作用，证明了相互作用的功能。讨论了这种相互作用的可能意义。
