Crystal structure of the Haemophilus influenzae Hap adhesin reveals an intercellular oligomerization mechanism for bacterial aggregation
Crystal structure of the Haemophilus influenzae Hap adhesin reveals an intercellular oligomerization mechanism for bacterial aggregation
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流感嗜血杆菌 Hap 粘附素的晶体结构揭示了细菌聚集的细胞间寡聚机制
DOI：
10.1038/emboj.2011.279
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发表时间：
2011-09-14
期刊：
影响因子：
11.4
通讯作者：
St Geme, Joseph W., III
中科院分区：
文献类型：
--
作者：
Meng, Guoyu;Spahich, Nicole;St Geme, Joseph W., III
细菌生物膜是自然界中常见的复杂微生物群落，越来越被认为是细菌毒力的重要决定因素。然而，细菌聚集和最终形成生物膜的结构决定因素尚未明确。在革兰氏阴性菌中，细胞外蛋白的一个主要亚群称为自相关自转运蛋白（SAATs），可以介导细胞间的粘附并促进生物膜的形成。在这项研究中，我们使用流感嗜血杆菌Hap自转运体作为SAAT原型来了解细菌如何相互关联。通过x射线晶体学测定流感病毒Hap(S)乘客结构域（包含SAAT结构域）的晶体结构为2.2 Å，揭示了细胞间相互作用的前所未有的细胞间寡聚化机制。c端SAAT结构域可折叠成三角形棱柱状结构，通过F1-F2边和F2面介导Hap-Hap二聚化和更高程度的多聚化。细胞间多聚可以产生巨大的埋藏表面，这是克服细胞间排斥力所必需的，导致细菌细胞间相互作用和形成复杂的微菌落。
Bacterial biofilms are complex microbial communities that are common in nature and are being recognized increasingly as an important determinant of bacterial virulence. However, the structural determinants of bacterial aggregation and eventual biofilm formation have been poorly defined. In Gram-negative bacteria, a major subgroup of extracellular proteins called self-associating autotransporters (SAATs) can mediate cell-cell adhesion and facilitate biofilm formation. In this study, we used the Haemophilus influenzae Hap autotransporter as a prototype SAAT to understand how bacteria associate with each other. The crystal structure of the H. influenzae Hap(S) passenger domain (harbouring the SAAT domain) was determined to 2.2 Å by X-ray crystallography, revealing an unprecedented intercellular oligomerization mechanism for cell-cell interaction. The C-terminal SAAT domain folds into a triangular-prism-like structure that can mediate Hap-Hap dimerization and higher degrees of multimerization through its F1-F2 edge and F2 face. The intercellular multimerization can give rise to massive buried surfaces that are required for overcoming the repulsive force between cells, leading to bacterial cell-cell interaction and formation of complex microcolonies.