Crystal structure of the mucin-binding domain of Spr1345 from Streptococcus pneumoniae
Crystal structure of the mucin-binding domain of Spr1345 from Streptococcus pneumoniae
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肺炎链球菌 Spr1345 粘蛋白结合域的晶体结构
DOI：
10.1016/j.jsb.2010.10.016
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发表时间：
2011-04-01
影响因子：
3
通讯作者：
Chen, Yuxing
中科院分区：
文献类型：
--
作者：
Du, Yang;He, Yong-Xing;Chen, Yuxing
肺炎链球菌 R6 的表面蛋白 Spr1345 是一种 22 kDa 粘蛋白结合蛋白 (MucBP)，参与人肺和呼吸道的粘附和定植。它由粘蛋白结合结构域 (MucBD) 和富含脯氨酸的结构域 (PRD) 组成，后跟 LPxTG 基序，该基序被分选酶识别和切割，形成 171 个残基 (MF171) 的成熟形式，锚定在细胞壁上。我们发现单独的 MucBD 具有与成熟形式相当的体外粘蛋白结合亲和力，并且可以在人肺癌 A549 细胞的表面特异性富集。利用单波长反常色散 (SAD) 定相方法和碘信号，我们以 2.0 埃分辨率解析了 MucBD 的晶体结构，这是病原菌 MucBD 的第一个结构。整体结构采用类似免疫球蛋白的折叠，呈细长的棒状，由6条反向平行的β链和一个长环组成。结构比较表明保守的C端部分可能参与粘蛋白的识别。这些发现为粘蛋白介导的宿主-病原体相互作用提供了结构见解，这可能有助于设计针对肺炎球菌引起的人类疾病的新型疫苗和抗生素药物。 (C) 2010 Elsevier Inc. 保留所有权利。
The surface protein Spr1345 from Streptococcus pneumoniae R6 is a 22-kDa mucin-binding protein (MucBP) involved in adherence and colonization of the human lung and respiratory tract. It is composed of a mucin-binding domain (MucBD) and a proline-rich domain (PRD) followed by an LPxTG motif, which is recognized and cleaved by sortase, resulting in a mature form of 171 residues (MF171) that is anchored to the cell wall. We found that the MucBD alone possesses comparable in vitro mucin-binding affinity to the mature form, and can be specifically enriched at the surface of human lung carcinoma A549 cells. Using single-wavelength anomalous dispersion (SAD) phasing method with the iodine signals, we solved the crystal structure of the MucBD at 2.0 angstrom resolution, the first structure of MucBDs from pathogenic bacteria. The overall structure adopts an immunoglobulin-like fold with an elongated rod-like shape, composed of six anti-parallel beta-strands and a long loop. Structural comparison suggested that the conserved C-terminal moiety may participate in the recognition of mucins. These findings provided structural insights into host-pathogen interaction mediated by mucins, which might be useful for designing novel vaccines and antibiotic drugs against human diseases caused by pneumococci. (C) 2010 Elsevier Inc. All rights reserved.