4Y5J

Drosophila melanogaster Mini spindles TOG3

Summary for 4Y5J

• Entry DOI: 10.2210/pdb4y5j/pdb
• Descriptor: MINI SPINDLES TOG3 (2 entities in total)
• Functional Keywords: xmap215, tog, microtubule polymerization, protein binding
• Biological source: Drosophila melanogaster (Fruit fly)
• Total number of polymer chains: 1
• Total formula weight: 27337.44

Authors

Slep, K.C.,Howard, A.E. (deposition date: 2015-02-11, release date: 2015-03-11, Last modification date: 2024-02-28)

Primary citation

Howard, A.E.,Fox, J.C.,Slep, K.C.
Drosophila melanogaster Mini Spindles TOG3 Utilizes Unique Structural Elements to Promote Domain Stability and Maintain a TOG1- and TOG2-like Tubulin-binding Surface.
J.Biol.Chem., 290:10149-10162, 2015

PubMed Abstract: Microtubule-associated proteins regulate microtubule (MT) dynamics spatially and temporally, which is essential for proper formation of the bipolar mitotic spindle. The XMAP215 family is comprised of conserved microtubule-associated proteins that use an array of tubulin-binding tumor overexpressed gene (TOG) domains, consisting of six (A-F) Huntingtin, elongation factor 3, protein phosphatase 2A, target of rapamycin (HEAT) repeats, to robustly increase MT plus-end polymerization rates. Recent work showed that TOG domains have differentially 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 Mini spindles (Msps) TOG3. Msps TOG3 has two unique features as follows: the first is a C-terminal tail that stabilizes the ultimate four HEAT repeats (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 similarly conserved tubulin-binding intra-HEAT loop residues to engage α- and β-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.

PubMed: 25720490
DOI: 10.1074/jbc.M114.633826

Experimental method

X-RAY DIFFRACTION (2.303 Å)