CryoEM structure of human MICAL1, the novel multidomain flavoenzyme participating in actin cytoskeleton dynamics

MICALs form a family of mainly cytosolic multidomain enzymes that control actin cytoskeleton dynamics. They are peculiar actin-binding proteins as they cause F-actin depolymerisation by oxidation of actin residues thanks to the H2O2-producing NADPH oxidase activity of the N-terminal flavoprotein domain, which is enhanced in the MICAL-F-actin complex. The catalytic domain is followed by several domains, responsible of the control of the activity upon interaction with regulating small molecules and proteins. MICALs participate in cell differentiation, migration, division, vesicle trafficking and even gene expression through their actin depolymerising activity or H2O2 production leading to oxidation of largely unknown target proteins. Elucidating the 3D structure of MICAL1 by cryoEM, will clarify the hypothesised peculiar mode of regulation of the activity, and will be key to devise ways to modulate the enzyme activity in the context of diseases like cancer and neurological disorders.