fH2

FH2 stands for formin homology 2, a conserved protein domain found in formins, a family of actin-regulating proteins in eukaryotes. The FH2 domain is typically about 400 amino acids in length and forms the core actin-binding module that supports filament nucleation and processive elongation. It is commonly paired with the adjacent FH1 proline-rich domain, which helps recruit profilin–actin complexes to the growing filament. FH2 is present in many formins, including DIAPH1 (mDia1) and yeast Bni1, and is central to the way formins control actin dynamics.

Structure and function: The FH2 domain often functions as a constitutive dimer. It binds to the barbed end of an actin filament and forms a loose, two-armed interface that “stays” at the growing end as new actin subunits add. This processive capping allows ongoing elongation without complete dissociation. The FH2 domain can also contribute to actin nucleation, particularly in cooperation with other domains or factors, enabling the initial formation of new filaments.

Regulation: Formin activity, including that of FH2-containing proteins, is commonly regulated by autoinhibition involving DID and DAD domains. Activation can be driven by Rho family GTPases or other signals, which relieve autoinhibition and enable FH2-mediated elongation. The FH1 domain aids elongation by recruiting profilin–actin, accelerating monomer delivery to the growing barbed end.

Biological role: FH2-containing formins organize the actin cytoskeleton to influence cell shape, polarity, migration, cytokinesis, and vesicle trafficking. The domain is studied across organisms, from yeast to humans, and remains a focal point in understanding cytoskeletal regulation.