3O4X

Crystal structure of complex between amino and carboxy terminal fragments of mDia1

Summary for 3O4X

• Entry DOI: 10.2210/pdb3o4x/pdb
• Descriptor: Protein diaphanous homolog 1 (3 entities in total)
• Functional Keywords: autoinhibition, actin nucleator, actin binding, protein binding
• Biological source: Mus musculus (mouse); More
• Cellular location: Cell membrane: O08808 O08808
• Total number of polymer chains: 8
• Total formula weight: 367465.11

Authors

Eck, M.J.,Nezami, A.,Toms, A.V. (deposition date: 2010-07-27, release date: 2010-10-13, Last modification date: 2024-11-06)

Primary citation

Nezami, A.,Poy, F.,Toms, A.,Zheng, W.,Eck, M.J.
Crystal structure of a complex between amino and carboxy terminal fragments of mDia1: insights into autoinhibition of diaphanous-related formins.
Plos One, 5:e12992-e12992, 2010

PubMed Abstract: Formin proteins direct the nucleation and assembly of linear actin filaments in a variety of cellular processes using their conserved formin homology 2 (FH2) domain. Diaphanous-related formins (DRFs) are effectors of Rho-family GTPases, and in the absence of Rho activation they are maintained in an inactive state by intramolecular interactions between their regulatory N-terminal region and a C-terminal segment referred to as the DAD domain. Although structures are available for the isolated DAD segment in complex with the interacting region in the N-terminus, it remains unclear how this leads to inhibition of actin assembly by the FH2 domain. Here we describe the crystal structure of the N-terminal regulatory region of formin mDia1 in complex with a C-terminal fragment containing both the FH2 and DAD domains. In the crystal structure and in solution, these fragments form a tetrameric complex composed of two interlocking N+C dimers. Formation of the tetramer is likely a consequence of the particular N-terminal construct employed, as we show that a nearly full-length mDia1 protein is dimeric, as are other autoinhibited N+C complexes containing longer N-terminal fragments. The structure provides the first view of the intact C-terminus of a DRF, revealing the relationship of the DAD to the FH2 domain. Delineation of alternative dimeric N+C interactions within the tetramer provides two general models for autoinhibition in intact formins. In both models, engagement of the DAD by the N-terminus is incompatible with actin filament formation on the FH2, and in one model the actin binding surfaces of the FH2 domain are directly blocked by the N-terminus.

PubMed: 20927338
DOI: 10.1371/journal.pone.0012992

Experimental method

X-RAY DIFFRACTION (3.2 Å)