An unconventional TOG domain is required for CLASP localization

Area of Science:

• Cell Biology
• Structural Biology
• Molecular Cell Biology

Background:

• Cytoplasmic linker-associated proteins (CLASPs) are microtubule-associated proteins essential for microtubule dynamics.
• CLASPs regulate microtubule growth by promoting rescue and suppressing catastrophe.
• Their function involves tumor overexpressed gene (TOG) domains and a conserved C-terminal domain (CTD) for protein interactions.

Purpose of the Study:

• To structurally characterize the conserved C-terminal domain (CTD) of CLASPs.
• To elucidate the structural basis for CLASP's diverse subcellular localizations and interactions.

Main Methods:

• Structural modeling of the CLASP CTD.
• Identification of key residues involved in protein interactions.
• Analysis of CLASP interactions in migrating and dividing cells.

Main Results:

• The CLASP CTD can be structurally modeled as a TOG domain.
• A conserved surface-exposed arginine residue is critical for CTD interactions with partner proteins.
• This structural insight explains how CLASPs are directed to various subcellular locations.

Conclusions:

• The CLASP CTD shares structural similarity with TOG domains.
• A specific arginine residue in the CTD is vital for mediating interactions with binding partners.
• This provides a structural mechanism for CLASP's role in cell migration, Golgi organization, and chromosome segregation.