Key result
EPR and DSC experiments revealed that mDia1-FH2 has a flexible structure with a major temperature-induced conformational change at 41°C, and its binding destabilizes actin filaments.
The study demonstrates that the formin FH2 domain has a flexible structure and its binding destabilizes actin filaments, which is likely important for its biological function in regulating the actin cytoskeleton.
No immediate clinical implications; leaves open whether mDia1-FH2 flexibility modulates actin in vivo.
Formins are highly conserved proteins that are essential in the formation and regulation of the actin cytoskeleton. The formin homology 2 (FH2) domain is responsible for actin binding and acts as an important nucleating factor in eukaryotic cells. In this work EPR and DSC were used to investigate the properties of the mDia1-FH2 formin fragment and its interaction with actin. MDia1-FH2 was labeled with a maleimide spin probe (MSL). EPR results suggested that the MSL was attached to a single SH group in the FH2. In DSC and temperature-dependent EPR experiments we observed that mDia1-FH2 has a flexible structure and observed a major temperature-induced conformational change at 41 °C. The results also confirmed the previous observation obtained by fluorescence methods that formin binding can destabilize the structure of actin filaments. In the EPR experiments the intermolecular connection between the monomers of formin dimers proved to be flexible. Considering the complex molecular mechanisms underlying the cellular roles of formins this internal flexibility of the dimers is probably important for manifestation of their biological functions.
No takes yet. Share an insight, caveat, or question.
Kupi et al. (2013) studied this question. mDia1-FH2 formin fragment was evaluated on Conformational changes and interaction with actin. EPR and DSC experiments revealed that mDia1-FH2 has a flexible structure with a major temperature-induced conformational change at 41°C, and its binding destabilizes actin filaments.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: