Valency conversion in the type 1 fimbrial adhesin of Escherichia coli.
Valency conversion in the type 1 fimbrial adhesin of Escherichia coli.
复制标题
大肠杆菌 1 型菌毛粘附素的化合价转换。
DOI：
10.1046/j.1365-2958.2001.02545.x
复制
发表时间：
2001
影响因子：
3.6
通讯作者：
Klemm,P
中科院分区：
文献类型：
--
作者：
Sokurenko,EV;Schembri,MA;Trintchina,E;Kjaergaard,K;Hasty,DL;Klemm,P
FimH蛋白是一种1型凝集素样粘附亚基，或甘露糖敏感性菌毛，存在于大多数大肠杆菌菌株的表面。所有天然存在的FimH变体均表现出保守的甘露三糖特异性（即多价）结合。在这里，我们证明了用1C型菌毛粘附素FocH的相应片段替换FimH菌毛蛋白结构域内的残基185-279导致多价甘露三糖特异性结合特性的丧失，伴随着获得独特的单甘露糖特异性（即单价）结合能力。表达单价杂交粘附素的细菌能够与尿路上皮组织培养细胞和豚鼠红细胞强烈结合。然而，它们不能凝集酵母菌或结合人口腔细胞--这些功能很容易由E.大肠杆菌表达甘露三糖特异性FimH变体。基于不同结构的抑制化合物的相对效力，单价FimH-FocH粘附素内的受体结合位点具有延伸的结构，其总体构型类似于天然来源的多价FimH内的构型。单甘露糖特异性表型也可以通过位于FimH的凝集素结构域内但远离受体结合位点的单点突变E89 K来引起。结构改变通过对结合口袋的远端效应影响FimH粘附素的受体结合价，显然是通过影响FimH四级结构。
FimH protein is a lectin‐like adhesive subunit of type 1, or mannose‐sensitive, fimbriae that are found on the surface of mostEscherichia colistrains. All naturally occurring FimH variants demonstrate a conserved mannotriose‐specific (i.e. multivalent) binding. Here, we demonstrate that replacement of residues 185–279 within the FimH pilin domain with a corresponding segment of the type 1C fimbrial adhesin FocH leads to a loss of the multivalent mannotriose‐specific binding property accompanied by the acquisition of a distinct monomannose‐specific (i.e. monovalent) binding capability. Bacteria expressing the monovalent hybrid adhesins were capable of binding strongly to uroepithelial tissue culture cells and guinea pig erythrocytes. They could not, however, agglutinate yeast or bind human buccal cells – functions readily accomplished by theE. coli‐ expressing mannotriose‐specific FimH variants. Based on the relative potency of inhibiting compounds of different structures, the receptor binding site within monovalent FimH–FocH adhesin has an extended structure with an overall configuration similar to that within the multivalent FimH of natural origin. The monomannose‐only specific phenotype could also be invoked by a single point mutation, E89K, located within the lectin domain of FimH, but distant from the receptor binding site. The structural alterations influence the receptor‐binding valency of the FimH adhesin via distal effects on the combining pocket, obviously by affecting the FimH quaternary structure.