beta-Neurexin is a ligand for the Staphylococcus aureus MSCRAMM SdrC.
beta-Neurexin is a ligand for the Staphylococcus aureus MSCRAMM SdrC.
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β-系蛋白是金黄色葡萄球菌MSCRAMM SDRC的配体。
DOI：
10.1371/journal.ppat.1000726
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发表时间：
2010-01-15
期刊：
影响因子：
6.7
通讯作者：
Höök M
中科院分区：
文献类型：
--
作者：
Barbu EM;Ganesh VK;Gurusiddappa S;Mackenzie RC;Foster TJ;Sudhof TC;Höök M
革兰氏阳性细菌含有一系列表面蛋白，它们共价固定在生物体的细胞壁上。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着关键作用。 CWA 的一个亚家族具有共同的结构组织，其中多个结构域采用特征性 IgG 样折叠。已鉴定的微生物表面成分识别粘附基质分子 (MSCRAMM) 属于该亚科，来自金黄色葡萄球菌的 SdrC 也是如此。然而，之前并未鉴定出假定的 MSCRAMM SdrC 的相互作用宿主配体。我们筛选了噬菌体展示肽库，并鉴定了在 β-neurexin 中发现的与 SdrC 结合的肽序列。与已识别序列相对应的合成肽以及 β-neurexin 1 外域的重组形式以高亲和力和特异性结合 SdrC。此外，SdrC 在细菌上的表达大大增强了微生物对表面表达 β-neurexin 的培养哺乳动物细胞的粘附。综上所述，我们的实验结果表明 β-neurexin 是 SdrC 的配体。这种相互作用涉及位于哺乳动物蛋白 N 末端区域和 MSCRAMM 的 N2N3 结构域的特定序列。这两种蛋白质在适当的细胞上表达时相互作用的事实证明了相互作用的功能性。讨论了这种相互作用的可能影响。 金黄色葡萄球菌是一种机会性病原体，其特点是有可能在动物和人类中引起严重且危及生命的感染。这种细菌粘附宿主组织的能力被认为是疾病过程中的早期、重要事件，并有助于该生物体作为病原体的成功。对宿主组织的粘附是由名为 MSCRAMM（识别粘附基质分子的微生物表面成分）的细胞壁锚定蛋白亚家族介导的。我们实验室的工作表明，许多这些蛋白质具有共同的针对线性氨基酸序列的配体结合机制。基于这些观察，我们假设筛选随机肽的噬菌体展示文库可以鉴定 MSCRAMM 的受体。使用这种方法，我们证明假定的 MSCRAMM SdrC 识别神经元蛋白 β-neurexin 中的序列。此外，我们发现完整的 β-neurexin 1 是金黄色葡萄球菌 MSCRAMM SdrC 的功能配体。这种方法的成功实施可能为鉴定其他宿主配体和设计能够抑制这些相互作用的抗葡萄球菌疗法开辟道路。
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 β-neurexin that binds SdrC. A synthetic peptide corresponding to the identified sequence as well as a recombinant form of the β-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 β-neurexin on their surface. Taken together, our experimental results demonstrate that β-neurexin is a ligand for SdrC. This interaction involves a specific sequence located in the N-terminal region of the mammalian protein and the N2N3 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. Staphylococcus aureus is an opportunistic pathogen, distinguished by its potential to cause serious and life-threatening infections in animals and humans. The ability of this bacterium to adhere to host tissues is considered an early, essential event in the disease process and contributes to the success of the organism as a pathogen. Adherence to host tissues is mediated by a subfamily of cell-wall anchored proteins named MSCRAMMs (microbial surface component recognizing adhesive matrix molecules). Work in our laboratory suggested that many of these proteins share a common ligand binding mechanism targeting linear amino acid sequences. Based on these observations, we hypothesized that screening a phage display library of random peptides may identify receptors for MSCRAMMs. Using this method, we demonstrate that the putative MSCRAMM SdrC recognizes a sequence in the neuronal protein β-neurexin. Furthermore, we show that intact β-neurexin 1 is a functional ligand for the S. aureus MSCRAMM SdrC. Successful implementation of this approach may open avenues for the identification of additional host ligands and the design of anti-staphylococcal therapeutics able to inhibit these interactions.
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影响因子：
6.7
作者：
Ganesh VK;Rivera JJ;Smeds E;Ko YP;Bowden MG;Wann ER;Gurusiddappa S;Fitzgerald JR;Höök M
通讯作者：
Höök M
影响因子：
4.8
作者：
McAleese, FM;Walsh, EJ;Foster, TJ
通讯作者：
Foster, TJ
DOI：
10.1099/00221287-144-12-3387
发表时间：
1998-12-01
期刊：
MICROBIOLOGY-UK
影响因子：
--
作者：
Josefsson, E;McCrea, KW;Foster, TJ
通讯作者：
Foster, TJ
DOI：
10.1107/s0907444998012426
发表时间：
1999-02-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Deivanayagam, CCS;Perkins, S;Narayana, SVL
通讯作者：
Narayana, SVL
影响因子：
4.8
作者：
Bowden, M. Gabriela;Heuck, Alejandro P.;Hook, Magnus
通讯作者：
Hook, Magnus