Interaction of
RhoA GTPase with its effector p160Rock
Radovan
DVORSKY1, Lars BLUMENSTEIN1, Mohammad R. AHMADIAN1
1 Max-Planck-Institute of Molecular Physiology, Department Structural
Biology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany
The GTP-binding
proteins (or Rho-GTPases) of the Rho-family regulate a variety of cellular
processes in all eukaryotic cells, ranging from cytoskeletal reorganization and
cell motility to gene transcription in response to external stimuli [1]. To
date, 19 different mammalian Rho-GTPases have been identified from which Cdc42,
Rac1 and RhoA are the most extensively characterised members of the Rho-family.
The function of Rho-GTPases depends on the guanine nucleotide-bound state. As
molecular switches Rho-GTPases cycle between an inactive GDP-bound state and an
active GTP-bound state, which is controlled by numerous cellular proteins.
Active form of Rho-GTPases interact with their downstream targets, so-called
effector proteins, that are responsible for the diverse biological effects of
Rho-GTPases [2]. One of the best studied Rho-Effectors, the Ser/Thr kinase
p160Rock, plays a key role in actin–myosin filament assembly by activation of
signalling molecules involved in various biological processes [3].
We will present
the structure of the complex of RhoA GTPase with the Rho-binding domain of
p160Rock. We found that the switching regions of RhoA molecule interacts with
C-terminal part of parallel coiled-coil formed by Rho-binding domains. Such an
arrangement of the complex will be discussed with respect to the general
switching mechanism of GTPases and their interaction with downstream effectors.
1.
A. Hall, Science 279 (1998) 509–514.
2. A.
L. Bishop & A. Hall, Biochem J.
348 (2000) 241-255.
3. M. Amano, Y. Fukata & K. Kaibuchi, Exp Cell Res.
261 (2000) 44-51.