Deciphering the actin structure-dependent preferential cooperative binding of cofilin

Area of Science:

• Biochemistry
• Molecular Biology
• Cell Biology

Background:

• The precise mechanism of cofilin binding and cluster formation on actin filaments is not fully understood.
• Cofilin plays a crucial role in actin dynamics, influencing filament severing and organization.

Purpose of the Study:

• To elucidate the structural basis for cofilin's preferential and cooperative binding to actin filaments.
• To investigate the role of actin filament structure, specifically helical twisting, in cofilin interactions.

Main Methods:

• Principal component analysis of actin structures (F-actin, C-actin, G-actin).
• High-speed atomic force microscopy (HS-AFM) to observe actin filament morphology.
• Comparison of cofilin binding under different conditions (e.g., lipid membrane attachment, inorganic phosphate presence).

Main Results:

• C-actin structures, not F-ADP-actin, are favored for cofilin binding.
• Shortened bare half helices near cofilin clusters exhibit an elongated mean axial distance (MAD) between actin protomers (5.0-6.3 nm).
• Inhibition of torsional motion (e.g., via lipid membrane attachment) more strongly inhibits cofilin binding than inorganic phosphate (Pi).

Conclusions:

• Actin protomers within shorter bare helical twists adopt C-actin-like structures with an elongated MAD.
• This C-actin-like conformation facilitates preferential and cooperative cofilin binding.
• Helical twisting and torsional rigidity significantly modulate cofilin-actin interactions.