InterPro domain: IPR036133

A group of microtubule-associated proteins called +TIPs (plus end trackingproteins), including EB1 (end-binding protein 1) family proteins, labelgrowing microtubules ends specifically in diverse organisms and are implicatedin spindle dynamics, chromosome segregation, and directing microtubules towardcortical sites. EB1 members have a bipartite composition: the N-terminal CHdomain ( IPR001715 ) mediates microtubule plus end localization and a C-terminal cargo binding domain (EB1-C) that captures cell polaritydeterminants. The EB1-C domain comprises a unique EB1-like sequence motif thatacts as a binding site for other +TIP proteins. It interacts with the carboxyterminus of the adenomatous polyposis coli (APC) tumor suppressor, a wellconserved +TIP phosphoprotein with a pivotal function in cell cycleregulation. Another binding partner of the EB1-C domain is the well conserved+TIP protein dynactin, a component of the large cytoplasmic dynein/dynactincomplex [ 1 , 2 , 3 ].

The ~80-residue EB1-C domain starts with a long smoothly curved helix(alpha1), which is followed by a hairpin connection leading to a short secondhelix (alpha2) running antiparallel to alpha1. The twoparallel alpha1 helices of the EB1-C domain dimer wrap around each other in aslightly left-handed supercoil. The two alpha2 helices run antiparallel tohelices alpha1 and form a similar fork in the opposite orientation and rotatedby 90 degrees. As a result, two helical segments from each monomer form a four-helixbundle. The side chain forming the hydrophobic core of this bundle are highlyconserved [ 4 , 4 , 4 ].

Some protein known to contain an EB1-C domain are listed below:

• Yeast protein BIM1.
• Fission yeast microtubule integrity protein mal3.
• Vertebrate microtubule-associated protein RP/EB family member 1 (EB1).
• Vertebrate microtubule-associated protein RP/EB family member 2 (EB2 or RP1).
• Vertebrate microtubule-associated protein RP/EB family member 3 (EBF3).

1. A novel localization pattern for an EB1-like protein links microtubule dynamics to endomembrane organization. Curr. Biol. 13, 1991-7
2. Structural determinants for EB1-mediated recruitment of APC and spectraplakins to the microtubule plus end. J. Cell Biol. 168, 587-98
3. Structural insights into the EB1-APC interaction. EMBO J. 24, 261-9
4. Structural basis for the activation of microtubule assembly by the EB1 and p150Glued complex. Mol. Cell 19, 449-60