A structural and dynamic visualization of the interaction between MAP7 and microtubules

Area of Science:

• Cell Biology
• Structural Biology
• Biochemistry

Background:

• Microtubules (MTs) are crucial for eukaryotic cytoskeleton functions, including intracellular organization, organelle transport, and mitosis.
• Microtubule-associated proteins (MAPs) regulate MT functions through binding and interactions.
• Microtubule-associated protein 7 (MAP7) binds MTs and activates kinesin-1 transport, also stabilizing MTs via its MT-binding domain (MTBD).

Purpose of the Study:

• To elucidate the structural basis of the MAP7 MTBD interaction with the microtubule lattice at an atomic level.
• To understand how MAP7 binds to and potentially stabilizes microtubules.

Main Methods:

• Solid and solution-state nuclear magnetic resonance (NMR) spectroscopy.
• Electron microscopy (EM).
• Fluorescence anisotropy and isothermal titration calorimetry (ITC).

Main Results:

• Detailed atomic-level insights into the binding mode of MAP7 MTBD to microtubules.
• MAP7 binding involves interactions extending beyond a single tubulin dimer.
• Interactions with tubulin C-terminal tails contribute significantly to MAP7-MT complex formation.

Conclusions:

• The MAP7 MTBD utilizes a complex binding mode involving multiple tubulin subunits and their C-terminal tails.
• This interaction mechanism underlies MAP7's ability to bind and stabilize microtubules.
• Structural understanding of MAP7-MT interactions provides insights into cytoskeletal regulation and transport.