XMAP215-Dis1 family

The XMAP215/Dis1 family is a highly conserved group of microtubule-associated proteins (MAPs) in eukaryotic organisms. These proteins are unique MAPs because they primarily interact with the growing-end (plus-end) of microtubules. This special property classifies this protein family as plus-end tracking proteins (+TIPs).

The basic structure of the protein family consists of TOG (Tumor Overexpressed Gene) domains, ranging from 2-5 units. The family is categorized into three groups based on the number of TOG domains that specific protein contains. Higher eukaryotic organisms, categorized in the first group, contain five, N-terminus TOG domains and a variable region that connects to a C-terminal domain. These domains are highly conserved monomeric sequences. The second group consists of only the Caenorhabditis elegans protein zyg-9, which has three TOG domains. It is similar, though, to higher eukaryotes because of its variable region and C-terminal domain. The third group consists of lower eukaryotic organisms, mainly yeast, that contain only two TOG domains and a coiled-coil domain.

Thorough analysis of the TOG3 domain in zyg-9 provides a basic understanding of this domain that is conserved throughout all members of the XMAP215/Dis1 family. Each domain consists of six HEAT (Huntingtin, Elongation factor 3, the PR65/A subunit of protein phosphatase 2A and the lipid kinase Tor) repeat units that are adjacently aligned. Each HEAT molecule consists of two α helices that are connected by a single loop. These α helices form the wide, flat surface of the domain. The loops between HEAT repeats and between individual α helices run along the short side of the domain. This short region is necessary for binding to tubulin. An additional HEAT repeat, localized between the first and second HEAT repeat, is exclusive to the TOG3 domain in zyg-9 and the TOG5 domains in the first group family proteins.

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