5MCA

Crystal structure of FimH-LD R60P variant in the apo state

5MCA の概要

• エントリーDOI: 10.2210/pdb5mca/pdb
• 分子名称: Protein FimH, SULFATE ION (3 entities in total)
• 機能のキーワード: fimh, type 1 pilus, pilus, uti, urinary tract infection, bladder, escherichia coli, sugar binding protein
• 由来する生物種: Escherichia coli K-12
• 細胞内の位置: Fimbrium : P08191
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 17009.86

構造登録者

Jakob, R.P.,Rabbani, S.,Ernst, B.,Maier, T. (登録日: 2016-11-09, 公開日: 2017-12-06, 最終更新日: 2024-11-13)

主引用文献

Rabbani, S.,Fiege, B.,Eris, D.,Silbermann, M.,Jakob, R.P.,Navarra, G.,Maier, T.,Ernst, B.
Conformational switch of the bacterial adhesin FimH in the absence of the regulatory domain: Engineering a minimalistic allosteric system.
J. Biol. Chem., 293:1835-1849, 2018

PubMed Abstract: For many biological processes such as ligand binding, enzymatic catalysis, or protein folding, allosteric regulation of protein conformation and dynamics is fundamentally important. One example is the bacterial adhesin FimH, where the C-terminal pilin domain exerts negative allosteric control over binding of the N-terminal lectin domain to mannosylated ligands on host cells. When the lectin and pilin domains are separated under shear stress, the FimH-ligand interaction switches in a so-called catch-bond mechanism from the low- to high-affinity state. So far, it has been assumed that the pilin domain is essential for the allosteric propagation within the lectin domain that would otherwise be conformationally rigid. To test this hypothesis, we generated mutants of the isolated FimH lectin domain and characterized their thermodynamic, kinetic, and structural properties using isothermal titration calorimetry, surface plasmon resonance, nuclear magnetic resonance, and X-ray techniques. Intriguingly, some of the mutants mimicked the conformational and kinetic behaviors of the full-length protein and, even in absence of the pilin domain, conducted the cross-talk between allosteric sites and the mannoside-binding pocket. Thus, these mutants represent a minimalistic allosteric system of FimH, useful for further mechanistic studies and antagonist design.

PubMed: 29180452
DOI: 10.1074/jbc.M117.802942

実験手法

X-RAY DIFFRACTION (1.604 Å)