Myosin isoforms show unique conformations in the actin-bound state

Area of Science:

• Biochemistry
• Structural Biology
• Muscle Physiology

Background:

• Myosin isoforms exhibit distinct conformations in the absence of actin, including prehydrolysis and transition states.
• These states differ in actin-binding cleft closure and lever arm position, crucial for force generation.
• Previous studies utilized cryo-EM and structural fitting to analyze myosin-actin interactions.

Purpose of the Study:

• To investigate the conformations of actin-bound chicken skeletal muscle myosin subfragment-1 (S1).
• To compare actin-bound myosin conformations with available crystal structures.

Main Methods:

• Analysis of crystallographic data for multiple myosin isoforms.
• Computer-based fitting of crystal structures into 3D cryo-electron microscopy reconstructions.
• Examination of actin-bound chicken skeletal muscle S1 conformations.

Main Results:

• Actin-bound myosin isoforms adopt unique conformations not fully represented by crystal structures.
• These unique conformations feature a more tightly closed actin-binding cleft.
• The lever arm adopts a more downward position, and surface loops exhibit increased stability.

Conclusions:

• Myosin isoforms in a nucleotide-free, actin-bound state possess distinct structural characteristics.
• These findings suggest unique, stabilized actin-bound conformations for myosin.
• Understanding these conformations is key to elucidating myosin's mechanism of force generation.