Limits...
The bacterial fimbrial tip acts as a mechanical force sensor.

Aprikian P, Interlandi G, Kidd BA, Le Trong I, Tchesnokova V, Yakovenko O, Whitfield MJ, Bullitt E, Stenkamp RE, Thomas WE, Sokurenko EV - PLoS Biol. (2011)

Bottom Line: The conformation between the FimH pilin domain and the following FimG subunit of the tip is open and stable even when tensile force is applied, providing an extended lever arm for the hook unhinging under shear.Finally, the conformation between FimG and FimF subunits is highly flexible even in the absence of tensile force, conferring to the FimH adhesin an exploratory function and high binding rates.Comparison to other structures suggests that this property is common in unrelated bacterial and eukaryotic adhesive complexes that must function in dynamic conditions.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, University of Washington, Seattle, Washington, United States of America.

ABSTRACT
There is increasing evidence that the catch bond mechanism, where binding becomes stronger under tensile force, is a common property among non-covalent interactions between biological molecules that are exposed to mechanical force in vivo. Here, by using the multi-protein tip complex of the mannose-binding type 1 fimbriae of Escherichia coli, we show how the entire quaternary structure of the adhesive organella is adapted to facilitate binding under mechanically dynamic conditions induced by flow. The fimbrial tip mediates shear-dependent adhesion of bacteria to uroepithelial cells and demonstrates force-enhanced interaction with mannose in single molecule force spectroscopy experiments. The mannose-binding, lectin domain of the apex-positioned adhesive protein FimH is docked to the anchoring pilin domain in a distinct hooked manner. The hooked conformation is highly stable in molecular dynamics simulations under no force conditions but permits an easy separation of the domains upon application of an external tensile force, allowing the lectin domain to switch from a low- to a high-affinity state. The conformation between the FimH pilin domain and the following FimG subunit of the tip is open and stable even when tensile force is applied, providing an extended lever arm for the hook unhinging under shear. Finally, the conformation between FimG and FimF subunits is highly flexible even in the absence of tensile force, conferring to the FimH adhesin an exploratory function and high binding rates. The fimbrial tip of type 1 Escherichia coli is optimized to have a dual functionality: flexible exploration and force sensing. Comparison to other structures suggests that this property is common in unrelated bacterial and eukaryotic adhesive complexes that must function in dynamic conditions.

Show MeSH

Related in: MedlinePlus

Quantitative data from MD simulations.Bars filled with dots indicate averages of quantities measured during the 300 K simulations, while bars with angular hatching indicate averages from the last 2 ns of pulling runs. Error bars show standard deviations (SD). To highlight quantities with large SD, the error bar is thicker if the SD is larger than the average of all SDs of a given quantity. (a) Cα RMSD of pairwise adjacent domains. (b) Distance between the centers of mass of two adjacent domains. (c) Surface area buried between two adjacent domains. (d) Hinge and (e) twist angle between two adjacent domains, respectively. (f) Number of native side-chain contacts between two adjacent domains.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3091844&req=5

pbio-1000617-g004: Quantitative data from MD simulations.Bars filled with dots indicate averages of quantities measured during the 300 K simulations, while bars with angular hatching indicate averages from the last 2 ns of pulling runs. Error bars show standard deviations (SD). To highlight quantities with large SD, the error bar is thicker if the SD is larger than the average of all SDs of a given quantity. (a) Cα RMSD of pairwise adjacent domains. (b) Distance between the centers of mass of two adjacent domains. (c) Surface area buried between two adjacent domains. (d) Hinge and (e) twist angle between two adjacent domains, respectively. (f) Number of native side-chain contacts between two adjacent domains.

Mentions: Average and standard deviation of the number of native contacts during the 300 K runs, excluding the first 10 ns (see also Figure 4f).


The bacterial fimbrial tip acts as a mechanical force sensor.

Aprikian P, Interlandi G, Kidd BA, Le Trong I, Tchesnokova V, Yakovenko O, Whitfield MJ, Bullitt E, Stenkamp RE, Thomas WE, Sokurenko EV - PLoS Biol. (2011)

Quantitative data from MD simulations.Bars filled with dots indicate averages of quantities measured during the 300 K simulations, while bars with angular hatching indicate averages from the last 2 ns of pulling runs. Error bars show standard deviations (SD). To highlight quantities with large SD, the error bar is thicker if the SD is larger than the average of all SDs of a given quantity. (a) Cα RMSD of pairwise adjacent domains. (b) Distance between the centers of mass of two adjacent domains. (c) Surface area buried between two adjacent domains. (d) Hinge and (e) twist angle between two adjacent domains, respectively. (f) Number of native side-chain contacts between two adjacent domains.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3091844&req=5

pbio-1000617-g004: Quantitative data from MD simulations.Bars filled with dots indicate averages of quantities measured during the 300 K simulations, while bars with angular hatching indicate averages from the last 2 ns of pulling runs. Error bars show standard deviations (SD). To highlight quantities with large SD, the error bar is thicker if the SD is larger than the average of all SDs of a given quantity. (a) Cα RMSD of pairwise adjacent domains. (b) Distance between the centers of mass of two adjacent domains. (c) Surface area buried between two adjacent domains. (d) Hinge and (e) twist angle between two adjacent domains, respectively. (f) Number of native side-chain contacts between two adjacent domains.
Mentions: Average and standard deviation of the number of native contacts during the 300 K runs, excluding the first 10 ns (see also Figure 4f).

Bottom Line: The conformation between the FimH pilin domain and the following FimG subunit of the tip is open and stable even when tensile force is applied, providing an extended lever arm for the hook unhinging under shear.Finally, the conformation between FimG and FimF subunits is highly flexible even in the absence of tensile force, conferring to the FimH adhesin an exploratory function and high binding rates.Comparison to other structures suggests that this property is common in unrelated bacterial and eukaryotic adhesive complexes that must function in dynamic conditions.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, University of Washington, Seattle, Washington, United States of America.

ABSTRACT
There is increasing evidence that the catch bond mechanism, where binding becomes stronger under tensile force, is a common property among non-covalent interactions between biological molecules that are exposed to mechanical force in vivo. Here, by using the multi-protein tip complex of the mannose-binding type 1 fimbriae of Escherichia coli, we show how the entire quaternary structure of the adhesive organella is adapted to facilitate binding under mechanically dynamic conditions induced by flow. The fimbrial tip mediates shear-dependent adhesion of bacteria to uroepithelial cells and demonstrates force-enhanced interaction with mannose in single molecule force spectroscopy experiments. The mannose-binding, lectin domain of the apex-positioned adhesive protein FimH is docked to the anchoring pilin domain in a distinct hooked manner. The hooked conformation is highly stable in molecular dynamics simulations under no force conditions but permits an easy separation of the domains upon application of an external tensile force, allowing the lectin domain to switch from a low- to a high-affinity state. The conformation between the FimH pilin domain and the following FimG subunit of the tip is open and stable even when tensile force is applied, providing an extended lever arm for the hook unhinging under shear. Finally, the conformation between FimG and FimF subunits is highly flexible even in the absence of tensile force, conferring to the FimH adhesin an exploratory function and high binding rates. The fimbrial tip of type 1 Escherichia coli is optimized to have a dual functionality: flexible exploration and force sensing. Comparison to other structures suggests that this property is common in unrelated bacterial and eukaryotic adhesive complexes that must function in dynamic conditions.

Show MeSH
Related in: MedlinePlus