5IM8

Solution Structure of the Microtubule-Targeting COS Domain of MID1

Summary for 5IM8

• Entry DOI: 10.2210/pdb5im8/pdb
• NMR Information: BMRB: 30031
• Descriptor: E3 ubiquitin-protein ligase Midline-1 (1 entity in total)
• Functional Keywords: helix-loop-helix, microtubules, spectrin, ligase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 7755.72

Authors

Wright, K.M.,Du, H.,Dagnachew, M.,Massiah, M.A. (deposition date: 2016-03-05, release date: 2016-07-13, Last modification date: 2024-05-15)

Primary citation

Wright, K.M.,Du, H.,Dagnachew, M.,Massiah, M.A.
Solution structure of the microtubule-targeting COS domain of MID1.
Febs J., 283:3089-3102, 2016

PubMed Abstract: The human MID1 protein is required for the proper development during embryogenesis. Mutations of MID1 are associated with X-linked Opitz G syndrome, characterized by midline anomalies. MID1 associates with the microtubules and functions as an ubiquitin E3 ligase, targeting protein phosphatase 2A for ubiquitin-mediated regulation. The mechanism of microtubule association is not known. Recently, a 60-amino acid region termed the C-terminal subgroup One Signature (COS) box/domain was identified at the C-terminal end of the coiled-coil (CC) domain that facilitates microtubule localization. Insertion of the MID1 COS domain at the C-terminal end of the CC domain of a nonmicrotubule-associated TRIM protein confers microtubule localization. Here, we report the solution structure of the COS domain of MID1. The domain adopts a helix-loop-helix structure in which the N- and C-terminal ends are in close proximity. Hydrophobic residues stabilizing the interaction of the two α-helices form a central hydrophobic core. The loop separating the α-helices is structured, with two of its hydrophobic residues making contact with the central core. On the outer surface, positively charged residues form a distinct basic patch near the termini that we postulate is important for microtubule binding. A model of the structure of the preceding coiled-coil and COS domains (CC-COS) show that the COS domain forms a helical bundle at the C-terminal end of the CC domain similar to the spectrin-like fold observed with some known microtubule-binding proteins. Interestingly, the CC-COS domains bind to microtubules, demonstrating for the first time that MID1 can directly associate with the microtubules.

PubMed: 27367845
DOI: 10.1111/febs.13795

Experimental method

SOLUTION NMR