25.13:
Generation of Straight or Branched Actin Filaments
Depending on their function, actins can form straight bundles or branched filaments.
Straight actin filaments are generated by the dimeric protein formin, whose FH1 domain acts as a binding site for the profilin-ATP-actin complex. The donut-shaped FH2 domain initiates actin nucleation with two actin monomers.
The FH2 domain receives one actin monomer at a time from the FH1 domain, generating a straight filament.
Branched actin filaments are generated by the Arp2/3 complex.
The Arp2/3 complex binds with CDC42–activated nucleation-promoting factor with attached actin monomer.
The binding of Arp2/3 with NPFs alters its conformation allowing it to bind to the sides of a pre-existing actin filament for elongation.
Upon binding to the actin filament, NPFs add actin monomers to the activated Arp2/3 complex for nucleation before dissociating.
The elongation of the branched filament proceeds at a seventy-degree angle, forming a Y-shaped network.
25.13:
Generation of Straight or Branched Actin Filaments
The straight or branched structure formation of actin filaments is controlled by nucleating proteins such as the formins and Arp2/3 complex. Formin-mediated assembly results in straight filaments, whereas Arp2/3 protein complex-mediated assembly results in branched actin filaments.
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is activated through conformational changes that occur with the synergistic help of other proteins, such as the regulatory nucleation promoting factors or NPFs, actin filaments, an actin monomer, and ATP. The complex nucleates the formation of a branch or a daughter filament on an existing actin filament. Arp2 and Arp3 have a conserved surface similar to actin and are the first two subunits at the pointed end of the branch. The presence of these subunits promotes the binding of actin monomers to the complex and initiates the formation of the branch.
Formins
Formins are homodimers of polypeptides that consist of characteristic domains such as the FH2 domain. FH2 domains associate with each other from head to tail to form a donut-shaped dimer. This dimer nucleates the formation of straight actin filaments at the required site. Formins are responsible for forming the contractile ring that separates daughter cells during cytokinesis and actin filaments bundles in filopodia. As the filament grows, formins are processively or continuously associated with the growing barbed end to protect it from capping proteins. Formins have several isomers that are function-specific in some cases and cannot be interchanged. For example, in fission yeast, three separate isoforms nucleate the formation of actin filaments used in the contractile ring, actin cables, and mating, respectively.
Suggested Reading
- Pollard, T. D. (2007). Regulation of actin filament assembly by Arp2/3 complex and formins. Annu. Rev. Biophys. Biomol. Struct., 36, 451-477.
- Kovar, D. R. (2006). Molecular details of formin-mediated actin assembly. Current opinion in cell biology, 18(1), 11-17.
- Espinoza-Sanchez, S., Metskas, L. A., Chou, S. Z., Rhoades, E., & Pollard, T. D. (2018). Conformational changes in Arp2/3 complex induced by ATP, WASp-VCA, and actin filaments. Proceedings of the National Academy of Sciences, 115(37), E8642-E8651.