CONFORMATIONAL TRANSITION OF FORMIN DISORDERED REGION UPON PROFILIN BINDING

Abstract

Filopodia are essential for the development of neuronal growth cones, cell polarity and cell migration. Their protrusions are powered by actin filaments polymerization whose acceleration depends on the number of profilin-actins binding with the formin-FH1 domain. Biophysical characterization of the disordered formin-FH1 domain remains a challenge. We analyzed the conformational distribution of the mDia1-FH1 bound with one to six profilins. We found a coil-to-elongation transition in the FH1 domain. We propose a cooperative ?jack? model for the FH1 domain of formins stacked by profilin-actins. Isothermal titration calorimetry of profilin-FH1 binding showed it is an exothermal reaction and unveiled the possibility that the binding energy derived from proflin-FH1 binding could be exploited for formin motor function. Luminescent decay experiments further supported the conformational elongation of FH1 domain upon profilin binding with the observation of neighbor cooperativity that a bound profilin induces the neighbor residues to adopt an elongated conformation as well.