Formin homology 2 domain (FH2)

The Formin Homology 2 (FH2) domain is a highly conserved protein structural motif found in the formin family of proteins, which are key regulators of the actin and microtubule cytoskeleton [6, 10]. Functioning as a homodimer, the FH2 domain forms a characteristic donut-shaped structure that nucleates new actin filaments and processively tracks the growing barbed ends, protecting them from capping proteins while allowing for rapid elongation [8, 11]. Because formins are essential for fundamental cellular processes such as cytokinesis, cell migration, and morphogenesis, the FH2 domain has emerged as a potential therapeutic target for diseases characterized by aberrant cytoskeletal dynamics, including cancer metastasis and various genetic disorders [7, 16]. Small molecule inhibitors like SMIFH2 have been developed to block the FH2 domain activity, providing valuable tools for research and a starting point for drug discovery [1, 4]. However, achieving isoform specificity among the 15 human formins and avoiding off-target effects on other cytoskeletal proteins like myosins remain significant challenges in the development of formin-targeted therapies [1, 13].

Other names

FH2 domainFormin homology domain 2

Inhibition of actin nucleation and elongation by binding to the FH2 domain and preventing its interaction with actin monomers and filaments.