Practice question

Formin FH domains orchestrate assembly of long unbranched filaments in filopodia, dorsal stress fibers, yeast actin cables and contractile rings. FH2 domain 400 amino acids forms head to tail dimer with two actin binding sites, donut shaped ring encircling barbed end. Structural snapshots in different nucleotide states support stair stepping model where dimer steps onto newly added subunit without dissociating, remaining processively attached enabling continuous insertion while preventing CapZ binding. FH2 alone sufficient for nucleation in vitro, albeit slow, FH1 domain enhances efficiency. FH1 contains 10 to 15 polyproline motifs that bind profilin ATP actin via hydrophobic pocket, delivering monomers to barbed end at high local concentration, accelerating elongation up to 15 fold. This leaky capping behavior distinguishes formins from pure cappers. Thymosin beta4 sequesters monomers blocking both ends, profilin alone does not nucleate, FH2 does not recruit Arp2/3 machinery. Thus nucleation and persistent barbed association defines FH2 functionality and processive elongation mechanism.