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-Structure paper
タイトル | Evolutionary fine-tuning of conformational ensembles in FimH during host-pathogen interactions. |
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ジャーナル・号・ページ | Sci Adv, Vol. 3, Issue 2, Page e1601944, Year 2017 |
掲載日 | 2017年2月10日 |
![]() | Vasilios Kalas / Jerome S Pinkner / Thomas J Hannan / Michael E Hibbing / Karen W Dodson / Alex S Holehouse / Hao Zhang / Niraj H Tolia / Michael L Gross / Rohit V Pappu / James Janetka / Scott J Hultgren / ![]() |
PubMed 要旨 | 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 ...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. |
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手法 | X線回折 |
解像度 | 1.962 - 2.596 Å |
構造データ | ![]() PDB-5jqi: ![]() PDB-5jr4: |
化合物 | ![]() ChemComp-GOL: ![]() ChemComp-HOH: ![]() ChemComp-CA: |
由来 |
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![]() | SUGAR BINDING PROTEIN / lectin / immunoglobulin fold / carbohydrate binding protein / donor strand exchange |