Practice question

Length control at barbed end requires high affinity cappers preventing subunit addition. CapZ, known as capping protein CP alpha1 or alpha2 beta heterodimer, is major ubiquitous capper in mammals. Biochemical analysis shows binding Kd near 0.1 nanomolar, essentially irreversible without regulation. Crystal structure reveals mushroom shaped dimer where alpha subunit C terminal amphipathic helix binds hydrophobic pocket of ultimate actin subunit and beta subunit tentacle contacts penultimate subunit, sterically blocking monomer entry. In sarcomeres CapZ anchors thin filament plus end at Z disc line via interaction with nebulin and alpha actinin, maintaining thin filament length. In non muscle cells CapZ caps majority of free barbed ends, funneling polymerization to few uncapped ends created during signaling. Regulation involves PIP2 binding reducing affinity and CPI motif proteins CARMIL CD2AP and CKIP that allosterically uncap. Tropomyosin decorates sides stabilizing against cofilin, tropomodulin caps pointed ends, thymosin beta4 sequesters monomers, hence role of blocking further polymerization at plus end uniquely belongs to CapZ capping complex.