Actin filament dynamics at barbed ends: New structures, new insights

Figures

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  Figure 1. Structures of the barbed and pointed ends of actin filaments. (a) Canonical front- and side-facing views of an ATP-actin monomer (PDB ID: 1ATN). Due to their location when incorporated into filaments, subdomains 1 and 2 are referred to as the outer subdomains, and subdomains 3 and 4 are referred to as the inner subdomains. The side view of the monomer is superimposed with the structure of an internal, filamentous actin subunit (gray; PDB ID: 8F8P) via superposition of the inner subdomains (surface representation) to highlight differences in the relative orientations of the outer subdomains (ribbon representation). Gray and orange axes extend through the major axis of the outer subdomains. (b) Left, A structural model of an actin filament shown as a surface representation. Right, Side-facing views of the terminal subunits at the pointed (PDB ID: 8F8S) and barbed (PDB ID: 8F8R) ends (top and bottom) are superimposed with the structure of an internal, filamentous subunit, as in (a). This figure was adapted from Ref. [12] and made using ChimeraX [89]. (c) Slices through surface representations of the terminal, barbed end subunit (left) and an internal subunit (right) of an actin…

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  Figure 2. Formin regulates subunit addition at the barbed end. (a) Structural views of the dimeric FH2 domain of the formin mDia1 bound to the barbed end of an actin filament. The actin filament (dark gray and light gray) is shown as a surface and the formin (green and light green) is depicted using a ribbon representation (PDB ID: 8RU2). The actin subunits are labeled A1, A2, etc. The leading and trailing FH2 domains are labeled as FH2L and FH2T. (b) Schematic of filament elongation mediated by formin and profilin. Profilin-actin complexes (blue and yellow) bind polyproline tracts (pP tracts) encoded in the formin FH1 domain and are delivered to the barbed end. Incorporation of the incoming actin monomer at the barbed end requires undocking and translocation of the trailing FH2 domain (dark green). This is followed by dissociation of profilin from the actin and the polyproline tract. This figure was adapted from Ref. [21].

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  Figure 3. Complexes directly affecting barbed end dynamics. Cartoon depiction of dynamics associated with highlighted barbed end complexes. (a) Dynamics of the formin-capping protein (CP) decision complex (DC). The DC pauses filament growth until either CP or the formin dissociates from the barbed end. When CP dissociates, fast formin-mediated growth with profilin is promoted, whereas when the formin dissociates via steric competition with the α and β-tentacles of CP, CP prevents additional filament growth. (b) DC modulating proteins that promote actin filament growth. IQGAP1 and twinfilin further regulate DCs. IQGAP1 promotes barbed end displacement of CP, mDia1, or DCs. In contrast, twinfilin directly interacts with CP through CPI-motifs to displace CP and promote fast formin-mediated actin filament polymerization. (c) Complexes with traditional disassembly factors present at the barbed end. The top panel explores two proposed mechanisms concerning formin-cyclase-associated protein (CAP/Srv2) interactions in the presence of profilin (PFN1). In the first (depicted by the a), CAP/Srv2 displaces formin, while remaining associated with the barbed end. This promotes the depolymerization of…