XMAP215/Dis1 proteins, such as Alp14 and XMAP215, increase microtubules dynamic polymerization rates by recruiting soluble alpha/beta-tubulin via their conserved TOG domains to polymerizing microtubule plus ends [ PUBMED:21782439 PUBMED:24630105 … expand

XMAP215/Dis1 proteins, such as Alp14 and XMAP215, increase microtubules dynamic polymerization rates by recruiting soluble alpha/beta-tubulin via their conserved TOG domains to polymerizing microtubule plus ends [ PUBMED:21782439 PUBMED:24630105 ]. A TOG domain contains HEAT repeats.

This entry represents a structural domain with an armadillo (ARM)-like fold, consisting of a multi-helical fold comprised of two curved layers of α- helices arranged in a regular right-handed superhelix, where the repeats that make up this structure are arranged about a common axis [ PUBMED:10361086 ]. These superhelical structures present an extensive solvent-accessible surface that is well suited to binding large substrates such as proteins and nucleic acids. Domains and repeats with an ARM-like fold have been found in a number of proteins, including:

• ARM repeat domain, found in beta-catenins, importins, karyopherin and exportins.
• HEAT repeat domain, found in protein phosphatase 2a and initiation factor eIF4G.
• PHAT domain, found in the RNA-binding protein Smaug.
• Leucine-rich repeat variant, which contain an FeS cluster.
• Pumilio repeat domain, found in Pumilio protein.
• Regulatory subunit H of V-type ATPases.
• PBS lyase HEAT-like repeat.
• Mo25 protein.
• MIF4G domain-like, found in eukaryotic initiation factor eIF4G, translation initiation factor eIF-2b epsilon and nuclear cap-binding protein CBP80.
• The N-terminal domain of eukaryotic translation initiation factor 3 subunit 12.
• The C-terminal domain of leukotriene A4 hydrolase.
• The helical domain of phosphoinositide 3-kinase.
• The N-terminal fragment of adaptin alpha-C and beta subunits.
• The proximal leg segment and the linker domain of the clathrin heavy chain.

The sequence similarity among these different repeats or domains is low, however they exhibit considerable structural similarity. Furthermore, the number of repeats present in the superhelical structure can vary between orthologues, indicating that rapid loss/gain of repeats has occurred frequently in evolution. A common phylogenetic origin has been proposed for the armadillo and HEAT repeats [ PUBMED:11551174 ].

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