Interhead tension determines processivity across diverse N-terminal kinesins

Area of Science:

• Molecular biology
• Cellular transport
• Biophysics

Background:

• Kinesin motor proteins are crucial for intracellular transport.
• Processivity varies significantly among different kinesin families.
• Neck linker length is a potential factor influencing kinesin motor function.

Purpose of the Study:

• To investigate the role of neck linker length in kinesin motor processivity.
• To determine if neck linker mechanics, rather than head biochemistry, dictate processivity differences.
• To test the hypothesis that neck linker length variations cause inter-family processivity differences.

Main Methods:

• Systematic alteration of neck linker length in kinesin-1, -2, -3, -5, and -7 motors.
• Single-molecule fluorescence assays to measure run length and velocity.
• Biochemical analysis of catalytic head kinetics.

Main Results:

• Shortening neck linkers in kinesin-3 and kinesin-5 enhanced their processivity to match kinesin-1.
• A single residue substitution in kinesin-7's catalytic core also increased processivity.
• Processivity convergence occurred despite a 25-fold variation in motor speeds.

Conclusions:

• Kinesin motor processivity differences are primarily determined by neck linker domain length.
• Neck linker mechanics play a more significant role than ATP hydrolysis rate constants in unloaded processivity.
• This finding offers a unified explanation for processivity variations across diverse kinesin families.