ATP binding and crossbridge structure in muscle

Area of Science:

• Muscle physiology
• Biochemistry
• Molecular motor function

Background:

• Actin-myosin crossbridge cycling is fundamental to muscle contraction.
• Nucleotide binding to myosin is known to regulate crossbridge states.
• The precise structural changes of myosin during the power-stroke are not fully elucidated.

Purpose of the Study:

• To investigate if myosin alone, independent of actin, exhibits nucleotide-dependent structural changes.
• To determine if myosin's structural rearrangements are responsible for the power-stroke mechanism.
• To explore the role of myosin head orientation in muscle force generation.

Main Methods:

• Extraction of thick filaments from insect flight muscle.
• Analysis of crossbridge arrangement under varying nucleotide conditions (ATP vs. rigor).
• Comparison of structural periodicity in isolated thick filaments versus intact muscle fibers.

Main Results:

• Insect flight muscle myosin exhibits a periodic crossbridge arrangement in the presence of ATP, mimicking relaxed muscle.
• This ordered arrangement is reversibly lost under rigor-inducing conditions.
• Myosin's structural state is dependent on nucleotide binding, even in isolation.

Conclusions:

• Myosin's structural plasticity is key to the power-stroke mechanism.
• The power-stroke likely involves alterations in the myosin head's steric relationship with both thick and thin filaments.
• Myosin's intrinsic nucleotide-dependent conformational changes contribute significantly to muscle contraction.