Structural Insights of WHAMM's Interaction with Microtubules by Cryo-EM

Area of Science:

• Cell Biology
• Molecular Biology
• Biophysics

Background:

• WHAMM protein regulates membrane tubulation and intracellular trafficking.
• WHAMM binds membranes and microtubules (MTs), nucleating actin polymerization.
• MT binding represses WHAMM's actin nucleation activity.

Purpose of the Study:

• To elucidate the mechanism of WHAMM interaction with microtubules.
• To understand how WHAMM coordinates actin and MT networks.

Main Methods:

• Cryo-electron microscopy to determine WHAMM MT-binding motif (MBM) structure.
• Chemical cross-linking and mass spectrometry to verify interactions.
• Analysis of conformational changes in WHAMM upon MT binding.

Main Results:

• WHAMM interacts with αβ-tubulin via a peptide motif in its MT-binding domain.
• High-resolution structure of WHAMM's MBM assembled on MTs was reconstructed.
• A conformational switch of the MBM between MT-bound and non-bound states was identified.

Conclusions:

• WHAMM utilizes a specific motif to bind MTs, influencing its actin nucleation activity.
• Structural and biochemical data reveal WHAMM's mechanism for coordinating cytoskeletal networks.
• These findings offer insights into membrane trafficking and remodeling regulation.