5JR4

Crystal structure of FimH A27V/V163A from E. coli UTI89 bound to FimG N-terminal extension

5JR4 の概要

• エントリーDOI: 10.2210/pdb5jr4/pdb
• 関連するPDBエントリー: 5JQI
• 分子名称: Type 1 fimbiral adhesin FimH, FimG N-terminal extension, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: lectin, immunoglobulin fold, carbohydrate binding protein, sugar binding protein, donor strand exchange
• 由来する生物種: Escherichia coli (strain UTI89 / UPEC); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 30683.21

構造登録者

Kalas, V.,Hultgren, S.J. (登録日: 2016-05-05, 公開日: 2017-02-22, 最終更新日: 2024-10-23)

主引用文献

Kalas, V.,Pinkner, J.S.,Hannan, T.J.,Hibbing, M.E.,Dodson, K.W.,Holehouse, A.S.,Zhang, H.,Tolia, N.H.,Gross, M.L.,Pappu, R.V.,Janetka, J.,Hultgren, S.J.
Evolutionary fine-tuning of conformational ensembles in FimH during host-pathogen interactions.
Sci Adv, 3:e1601944-e1601944, 2017

PubMed Abstract: Positive selection in the two-domain type 1 pilus adhesin FimH enhances fitness in urinary tract infection (UTI). We report a comprehensive atomic-level view of FimH in two-state conformational ensembles in solution, composed of one low-affinity tense (T) and multiple high-affinity relaxed (R) conformations. Positively selected residues allosterically modulate the equilibrium between these two conformational states, each of which engages mannose through distinct binding orientations. A FimH variant that only adopts the R state is severely attenuated early in a mouse model of uncomplicated UTI but is proficient at colonizing catheterized bladders in vivo or bladder transitional-like epithelial cells in vitro. Thus, the bladder habitat has barrier(s) to R state-mediated colonization possibly conferred by the terminally differentiated bladder epithelium and/or decoy receptors in urine. Together, our studies reveal the conformational landscape in solution, binding mechanisms, and adhesive strength of an allosteric two-domain adhesin that evolved "moderate" affinity to optimize persistence in the bladder during UTI.

PubMed: 28246638
DOI: 10.1126/sciadv.1601944

実験手法

X-RAY DIFFRACTION (2.596 Å)