Conformational dynamics of actin: effectors and implications for biological function

Abstract

Actin is a protein abundant in many cell types. Decades of investigations have provided evidence that it has many functions in living cells. The diverse morphology and dynamics of actin structures adapted to versatile cellular functions is established by a large repertoire of actin-binding proteins. The proper interactions with these proteins assume effective molecular adaptations from actin, in which its conformational transitions play essential role. This review attempts to summarise our current knowledge regarding the coupling between the conformational states of actin and its biological function.

Fig. 1. Overview of the structure and conformational dynamics of actin monomer and filament

(A) Crystal structure of the G-actin molecule. Actin subdomains are indicated by different colors and numbers according to Holmes et al (S1) amino acids 1–32, 70–144, 338–375; (S2) amino acids 33–69; (S3) amino acids 145–180, 270–337; (S4) amino acids 181–269 [Holmes et al., 1990]. The amino-, and carboxyl termini of the molecule are indicated by N and C, respectively. Orange-dotted boxes depict enlarged views of the nucleotide binding cleft with bound ATP (a), the structure of the hydrophobic loop (b, amino acids 262–274, rotated by 90° to the right with respect to the main axis of the monomer, shown by gray dashed-dotted line) and the DNase binding loop (c, amino acids 40–48). The schematic representation of the conformational dynamics on the basis of the normal mode analysis of G-actin is shown by blue arrows [Tirion and ben-Avraham, 1993]. The image was made on the basis of the crystal structure of rabbit skeletal muscle actin in complex with DNase I (PDB code 1ATN, [Kabsch et al., 1990]). (B) Helical organization of actin protomers in the filament. A structural model of a 13-mer F-actin was derived from Oda's F-actin protomer model (PDB code 2ZWH, [Oda et al., 2009]). The two linear strands of actin protomers composing the two-start right-handed long pitch helix are colored by dim and dark violet, respectively. The single-start left-handed short pith helix is assembled by alternating dim and dark actin protomers. The schematic representation of the conformational dynamics of F-actin is shown by blue arrows. The ribbon diagrams were obtained with Deep View/Swiss PDB Viewer.

Fig. 2. Summary of the conformational changes in actin

The table shows the corresponding correlation times and the suitable approaches for their investigation.

Fig. 3. Summary of the most commonly used spectroscopic approaches to study the conformational dynamics of actin

The formulation and parameters of transient phosphorescence emission anisotropy (TPA), time-dependent fluorescence emission anisotropy and conventional/saturation transfer (ST) EPR. Typical phosphorescence (1. inset)/fluorescence (2. inset) anisotropy decay (r(t)) of actin, and typical EPR (3. inset)/ST-EPR (4. inset) spectra of actin are shown. H is releated to the direction and the strength of the applied magnetic field. In phosphorescence/fluorescence emission anisotropy the kinetics of anisotropy decay, while in EPR/ST-EPR the shape of the spectrum characteristic for the conformational dynamics of the molecule. [Color figure can be viewed in the online issue which is available at http://wileyonlinelibrary.com.]

Fig. 4. The most common mutation sites in muscle actin

The most common mutation sites are labeled with one letter and ID number of the amino acids [Olson et al., ; van Wijk et al., ; Zhu et al., ; Ilkovski et al., ; Marston et al., 2004]. The ribbon structure of rabbit skeletal muscle actin (PDB code: 1ATN [Kabsch et al., 1990] is colored black at the mutated points.