Abstract:
:Diaphanous-related formins (DRFs) regulate dynamics of unbranched actin filaments during cell contraction and cytokinesis. DRFs are autoinhibited through intramolecular binding of a Diaphanous autoinhibitory domain (DAD) to a conserved N-terminal regulatory element. Autoinhibition is relieved through binding of the GTPase RhoA to the N-terminal element. We report the crystal structure of the dimeric regulatory domain of the DRF, mDia1. Dimerization is mediated by an intertwined six-helix bundle, from which extend two Diaphanous inhibitory domains (DIDs) composed of five armadillo repeats. NMR and biochemical mapping indicate the RhoA and DAD binding sites on the DID partially overlap, explaining activation of mDia1 by the GTPase. RhoA binding also requires an additional structurally independent segment adjacent to the DID. This regulatory construction, involving a GTPase binding site spanning a flexibly tethered arm and the inhibitory module, is observed in many autoinhibited effectors of Ras superfamily GTPases, suggesting evolutionary pressure for this design.
journal_name
Mol Celljournal_title
Molecular cellauthors
Otomo T,Otomo C,Tomchick DR,Machius M,Rosen MKdoi
10.1016/j.molcel.2005.04.002subject
Has Abstractpub_date
2005-04-29 00:00:00pages
273-81issue
3eissn
1097-2765issn
1097-4164pii
S1097-2765(05)01226-8journal_volume
18pub_type
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