Interactions between motor domains in kinesin-14 Ncd - a molecular dynamics study

Area of Science:

• Molecular biology
• Biophysics
• Structural biology

Background:

• Kinesin-14 Ncd is a dimeric protein crucial for cellular transport.
• Its motor domains (heads) are C-terminally located, and a lever-like stalk facilitates movement.
• The C-terminal region of the Ncd head is vital for its power stroke mechanism but poorly understood.

Purpose of the Study:

• To investigate the conformational dynamics of kinesin-14 Ncd.
• To elucidate the role of the C-terminal region in Ncd's motor function.
• To explore the structural basis of Ncd's power stroke.

Main Methods:

• Accelerated molecular dynamics simulations were employed.
• Simulations utilized crystal structures of Ncd, including a T436S mutant and wild-type protein.
• Conformational changes and stabilizing interactions were analyzed.

Main Results:

• A novel compact conformation of Ncd was identified.
• This state is stabilized by hydrogen bonds involving the C-terminal linker (residues 675-683).
• Formation of the compact state requires a C-terminus extending to at least residue 681 and involves stalk rotation.

Conclusions:

• The C-terminus length is critical for Ncd's conformational dynamics.
• A stable compact conformation, dependent on the C-terminus, may represent an early stage of the working stroke.
• This finding offers new insights into the kinesin-14 Ncd motor mechanism.