 |
PDBsum entry 2v52
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Structural protein/contractile protein
|
PDB id
|
|
|
|
2v52
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Molecular basis for g-Actin binding to rpel motifs from the serum response factor coactivator mal.
|
|
|
Authors
|
|
S.Mouilleron,
S.Guettler,
C.A.Langer,
R.Treisman,
N.Q.Mcdonald.
|
|
|
Ref.
|
|
Embo J, 2008,
27,
3198-3208.
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Abstract
|
|
|
Serum response factor transcriptional activity is controlled through
interactions with regulatory cofactors such as the coactivator MAL/MRTF-A
(myocardin-related transcription factor A). MAL is itself regulated in vivo by
changes in cellular actin dynamics, which alter its interaction with G-actin.
The G-actin-sensing mechanism of MAL/MRTF-A resides in its N-terminal domain,
which consists of three tandem RPEL repeats. We describe the first molecular
insights into RPEL function obtained from structures of two independent
RPEL(MAL) peptide:G-actin complexes. Both RPEL peptides bind to the G-actin
hydrophobic cleft and to subdomain 3. These RPEL(MAL):G-actin structures explain
the sequence conservation defining the RPEL motif, including the invariant
arginine. Characterisation of the RPEL(MAL):G-actin interaction by fluorescence
anisotropy and cell reporter-based assays validates the significance of
actin-binding residues for proper MAL localisation and regulation in vivo. We
identify important differences in G-actin engagement between the two RPEL(MAL)
structures. Comparison with other actin-binding proteins reveals an unexpected
similarity to the vitamin-D-binding protein, extending the G-actin-binding
protein repertoire.
|
|
|
|
|
|
|
