2006 APS March Meeting
Monday–Friday, March 13–17, 2006;
Baltimore, MD
Session Z4: Biopolymers
11:15 AM–2:15 PM,
Friday, March 17, 2006
Baltimore Convention Center
Room: 308
Sponsoring
Units:
DPOLY DBP
Chair: Michael Lang and Zuowei Wang, University of North Carolina
Abstract ID: BAPS.2006.MAR.Z4.1
Abstract: Z4.00001 : Bonds that strengthen under force
11:15 AM–11:51 AM
Preview Abstract
Abstract
Author:
Viola Vogel
(Swiss Federal Institute of Technology, ETH)
While the adhesive strength of most receptor-ligand
interactions is
exponentially reduced if strained, some receptor-ligand
complexes
exist that
strengthen under force which is the hallmark of catch bonds.
Although the
existence of catch bonds was theoretically predicted, the first
experimental
demonstrations of their existence were given only recently, i.e.
for the
bacterial adhesin FimH that is located at the tip of type I
fimbriae of \textit{E. coli} and
for p-selectin. In a major collaborative effort, we studied the
structural
origin by which the FimH-mannose bond is switched by force to a
high binding
state. Mutational studies were thereby combined with steered
molecular
dynamic simulations to decipher how force might affect protein
conformation.
Force-activation of FimH leads to a complex `stick-and-roll'
bacterial
adhesion behavior in which \textit{E. coli} preferentially rolls
over mannosylated surfaces
at low shear but increasingly sticks firmly as the shear is
increased.
Interesting similarities are further seen if comparing the
structural
mechanisms by which liganded FimH and liganded integrins are
switched to a
high binding state. This comparison was made possible by
docking
fibronectin's 10$^{th}$ type III module (fnIII$_{10})$ to
$\alpha
_{V}\beta _{3}$ integrin. $\alpha _{V}\beta _{3}$ can switch
from the ``closed'' $\alpha _{V}\beta _{3}$ integrin headpiece
to
the
``open'' conformation by opening the hinge angle between the
$\beta $A
domain and the hybrid domain of the $\beta $-integrin. The
``open'' state
has been implicated by many experimental laboratories to
correspond to the
activated state of integrins.
\newline
\newline
W. E. Thomas, E. Trintchina, M. Forero, V. Vogel, E. Sokurenko,
Bacterial
adhesion to target cells enhanced by shear-force, Cell, 109
(2002) 913.
\newline
W. E. Thomas, L. M. Nilsson, M. Forero, E. V. Sokurenko, V.
Vogel,
Shear-dependent `stick-and-roll' adhesion of type 1 fimbriated
\textit{Escherichia coli}, Molecular
Microbiology 53 (2004) 1545.
\newline
W. Thomas, M. Forero, O. Yakovenko, L. Nilsson, P. Vicini, E.
Sokurenko, V.
Vogel, Catch Bond Model Derived from Allostery Explains
Force-Activated
Bacterial Adhesion, Biophys. J, in press
\newline
E. Puklin-Faucher, M. Gao, K. Schulten, V. Vogel, How the
opening
of the
$\beta $A/hybrid domain hinge angle in the $\alpha _{v}\beta _
{3}$
integrin headpiece is regulated by the liganded MIDAS
conformation and by
ligand-mediated mechanical force, submitted.
To cite this abstract, use the following reference: http://meetings.aps.org/link/BAPS.2006.MAR.Z4.1