Abstract

The end binding homology (EBH) domain (Pfam accession code PF03271) is a small, approximately 50-residue protein module highly conserved in organisms from yeast to man. It is exclusively found in end binding (EB) proteins. EB proteins autonomously track growing microtubule plus ends and act as a hub within dynamic microtubule plus-end tracking protein (+TIP) networks. +TIPs constitute a diverse group of evolutionarily conserved microtubule-associated proteins that specifically accumulate at the ends of growing microtubules. They play important roles in essential cellular activities, including chromosome segregation, cell polarization and migration, organelle transport, and intracellular signalling.

The C-terminal EBH domain of EB proteins binds to an array of structurally and functionally unrelated +TIP binding partners, including the adenomatous polyposis coli (APC) tumor suppressor protein, the microtubule-actin crosslinking factor (MACF), the cytoplasmic linker protein (CLIP170), CLIP-associated proteins (CLASPs), the transmembrane protein stromal interaction molecule-1 (STIM1), the dynactin large subunit p150glued, and the mitotic centromere-associated kinesin (MCAK). SxIP motifs embedded within basic and Pro/Ser rich sequence regions of numerous +TIPs specifically bind to highly conserved residues shaping a hydrophobic groove in the EBH domain. Thus EBH domains are SxIP recognition domains. The EBH-SxIP interaction is used to target +TIPs to EBs at growing microtubule ends. Therefore, SxIP motifs act as general microtubule tip localization signals (MtLS).