Structural Basis for Mechanical Force Regulation of the Adhesin FimH via Finger Trap-like β Sheet Twisting

نویسندگان

  • Isolde Le Trong
  • Pavel Aprikian
  • Brian A. Kidd
  • Manu Forero-Shelton
  • Veronika Tchesnokova
  • Ponni Rajagopal
  • Victoria Rodriguez
  • Gianluca Interlandi
  • Rachel Klevit
  • Viola Vogel
  • Ronald E. Stenkamp
  • Evgeni V. Sokurenko
  • Wendy E. Thomas
چکیده

The Escherichia coli fimbrial adhesive protein, FimH, mediates shear-dependent binding to mannosylated surfaces via force-enhanced allosteric catch bonds, but the underlying structural mechanism was previously unknown. Here we present the crystal structure of FimH incorporated into the multiprotein fimbrial tip, where the anchoring (pilin) domain of FimH interacts with the mannose-binding (lectin) domain and causes a twist in the beta sandwich fold of the latter. This loosens the mannose-binding pocket on the opposite end of the lectin domain, resulting in an inactive low-affinity state of the adhesin. The autoinhibition effect of the pilin domain is removed by application of tensile force across the bond, which separates the domains and causes the lectin domain to untwist and clamp tightly around the ligand like a finger-trap toy. Thus, beta sandwich domains, which are common in multidomain proteins exposed to tensile force in vivo, can undergo drastic allosteric changes and be subjected to mechanical regulation.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Mechanism of allosteric propagation across a β‐sheet structure investigated by molecular dynamics simulations

The bacterial adhesin FimH consists of an allosterically regulated mannose-binding lectin domain and a covalently linked inhibitory pilin domain. Under normal conditions, the two domains are bound to each other, and FimH interacts weakly with mannose. However, under tensile force, the domains separate and the lectin domain undergoes conformational changes that strengthen its bond with mannose. ...

متن کامل

FimH forms catch bonds that are enhanced by mechanical force due to allosteric regulation.

The bacterial adhesive protein, FimH, is the most common adhesin of Escherichia coli and mediates weak adhesion at low flow but strong adhesion at high flow. There is evidence that this occurs because FimH forms catch bonds, defined as bonds that are strengthened by tensile mechanical force. Here, we applied force to single isolated FimH bonds with an atomic force microscope in order to test th...

متن کامل

Catch-bond mechanism of the bacterial adhesin FimH.

Ligand-receptor interactions that are reinforced by mechanical stress, so-called catch-bonds, play a major role in cell-cell adhesion. They critically contribute to widespread urinary tract infections by pathogenic Escherichia coli strains. These pathogens attach to host epithelia via the adhesin FimH, a two-domain protein at the tip of type I pili recognizing terminal mannoses on epithelial gl...

متن کامل

Bacterial Adhesion to Target Cells Enhanced by Shear Force

Surface adhesion of bacteria generally occurs in the presence of shear stress, and the lifetime of receptor bonds is expected to be shortened in the presence of external force. However, by using Escherichia coli expressing the lectin-like adhesin FimH and guinea pig erythrocytes in flow chamber experiments, we show that bacterial attachment to target cells switches from loose to firm upon a 10-...

متن کامل

In silico Study of Toll-Like Receptor 4 Binding Site of FimH from Uropathogenic Escherichia coli

  Introduction : The innate immune system as the first line of defense against the pathogens recognizes pathogen-associated molecular patterns (PAMPs) by Toll-Like Receptors (TLRs). Interaction of bacterial PAMPs by TLRs results in activation of innate and acquired immunity. FimH adhesin, a minor component of type 1 fimbriae encoded by Uropathogenic Escherichia coli (UPEC) is a PAMP of TLR4 tha...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Cell

دوره 141  شماره 

صفحات  -

تاریخ انتشار 2010