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Publication Abstract from PubMed

Microtubule-associated proteins (MAPs) regulate microtubule (MT) dynamics spatially and temporally, which is essential for proper formation of the bipolar mitotic spindle. The XMAP215 family are conserved MAPs that use an array of tubulin-binding tumor overexpressed gene (TOG) domains, consisting of six (A-F) HEAT repeats (HRs), to robustly increase MT plus-end polymerization rates. Recent work showed that TOG domains have differential, conserved architectures across the array, with implications for position-dependent TOG domain tubulin-binding activities and function within the XMAP215 MT polymerization mechanism. Although TOG domains 1, 2, and 4 are well-described, structural and mechanistic information characterizing TOG domains 3 and 5 is outstanding. Here we present the structure and characterization of Drosophila melanogaster Msps TOG3. Msps TOG3 has two unique features; the first is a C-terminal tail that stabilizes the ultimate four HRs, and the second is a unique architecture in HR B. Structural alignments of TOG3 with other TOG domain structures show that the architecture of TOG3 is most similar to TOG domains 1 and 2, and diverges from TOG4. Docking TOG3 onto recently solved Stu2 TOG1- and TOG2-tubulin complex structures suggests that TOG3 uses similar, conserved tubulin-binding intra-HEAT loop residues to engage alpha- and beta-tubulin. This indicates that TOG3 has maintained a TOG1- and TOG2-like TOG-tubulin binding mode despite structural divergence. The similarity of TOG domains 1-3 and the divergence of TOG4 suggest that a TOG domain array with polarized structural diversity may play a key mechanistic role in XMAP215-dependent MT polymerization activity.

Drosophila melanogaster Msps TOG3 utilizes unique structural elements to promote domain stability and maintain a TOG1- and TOG2-like tubulin-binding surface.,Howard AE, Fox JC, Slep KC J Biol Chem. 2015 Feb 26. pii: jbc.M114.633826. PMID:25720490^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.