Molecular basis of filamin A-FilGAP interaction and its impairment in congenital disorders associated with filamin A mutations.

ABSTRACT:

Background

Mutations in filamin A (FLNa), an essential cytoskeletal protein with multiple binding partners, cause developmental anomalies in humans.

Methodology/principal findings

We determined the structure of the 23rd Ig repeat of FLNa (IgFLNa23) that interacts with FilGAP, a Rac-specific GTPase-activating protein and regulator of cell polarity and movement, and the effect of the three disease-related mutations on this interaction. A combination of NMR structural analysis and in silico modeling revealed the structural interface details between the C and D beta-strands of the IgFLNa23 and the C-terminal 32 residues of FilGAP. Mutagenesis of the predicted key interface residues confirmed the binding constraints between the two proteins. Specific loss-of-function FLNa constru

SUBMITTER: Nakamura F 

PROVIDER: S-EPMC2654154 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature