Structural Biology of Actin: Interplay Between Molecular Assembly, Conformational Polymorphism and ATPase

Area of Science:

• Biochemistry
• Structural Biology
• Cell Biology

Background:

• Actin, a key muscle protein, also drives dynamic remodeling in non-muscle cells via ATP-dependent treadmilling.
• Actin polymerization and ATP hydrolysis yield distinct ADP-P_i (stable) and ADP (unstable) states.

Purpose of the Study:

• To investigate the structural basis of actin's distinct nucleotide-bound states.
• To elucidate the mechanisms of actin polymerization and ATP hydrolysis.

Main Methods:

• X-ray crystallography
• Cryo-electron microscopy (Cryo-EM)
• Analysis of Protein Data Bank (PDB) data

Main Results:

• Developed an F-actin model showing polymerization-induced domain rotation (G-form to F-form).
• Resolved cryo-EM structure of cofilin-decorated F-actin (C-form).
• Classified actin structures into G-, F-, C-, and O-forms, linking them to specific functions.

Conclusions:

• Actin's distinct conformations (G, F, C, O) are linked to nucleotide exchange, hydrolysis, and filament severing.
• High-resolution structures clarify the ATP hydrolysis pathway and ADP-P_i stability.
• Differences in conformational fluctuations, not global structure, distinguish actin's nucleotide states and their functional properties.