Formins are a conserved family of actin assembly-promoting factors with essential and diverse biological roles. Most of our biochemical understanding of formin effects on actin dynamics is derived from studies using formin fragments. In addition, all structural information on formins has been limited to fragments. This has left open key questions about the structure, activity and regulation of intact formin proteins. Here, we isolated full-length mouse mDia1 (mDia1-FL) and found that it forms tightly autoinhibited dimers that can only be partially activated by RhoA. We solved the structure of autoinhibited mDia1-FL using electron microscopy and single particle analysis. Docking of crystal structures into the three dimensional reconstruction revealed that the fork-shaped N-terminal diaphanous inhibitory domain-coiled coil domain region hangs over the ring-shaped formin homology (FH)2 domain, suggesting that autoinhibition results from steric obstruction of actin binding. Deletion of the C-terminal diaphanous autoregulatory domain extended mDia1 structure and activated it for actin assembly. Using total internal reflection fluorescence microscopy, we observed that RhoA-activated mDia1-FL persistently accelerated filament elongation in the presence of profilin similar to mDia1 FH1-FH2 fragment. These observations validate the known activities of FH1-FH2 fragments as reflecting those of the intact molecule. Our results further suggest that mDia1-FL does not readily snap back into the autoinhibited conformation and dissociate from growing filament ends, and thus additional factors may be required to displace formins and restrict filament length.
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 June 2012.
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#15,687,538
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#102,087
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Outputs of similar age from Cytoskeleton
#5
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Altmetric has tracked 24,851,605 research outputs across all sources so far. This one is in the 34th percentile – i.e., 34% of other outputs scored the same or lower than it.
So far Altmetric has tracked 535 research outputs from this source. They receive a mean Attention Score of 3.4. This one is in the 45th percentile – i.e., 45% of its peers scored the same or lower than it.
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