2HAK

Catalytic and ubiqutin-associated domains of MARK1/PAR-1

2HAK の概要

• エントリーDOI: 10.2210/pdb2hak/pdb
• 関連するPDBエントリー: 1Y8G 1ZMU 1ZMV 1ZMW
• 分子名称: Serine/threonine-protein kinase MARK1 (2 entities in total)
• 機能のキーワード: serine/threonine protein kinase; mark; par-1; kin1; uba domain, signaling protein, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane ; Peripheral membrane protein : Q9P0L2
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 301700.03

構造登録者

Marx, A.,Nugoor, C.,Mueller, J.,Panneerselvam, S.,Mandelkow, E.-M.,Mandelkow, E. (登録日: 2006-06-13, 公開日: 2006-07-11, 最終更新日: 2023-10-25)

主引用文献

Marx, A.,Nugoor, C.,Mueller, J.,Panneerselvam, S.,Timm, T.,Bilang, M.,Mylonas, E.,Svergun, D.I.,Mandelkow, E.-M.,Mandelkow, E.
Structural variations in the catalytic and ubiquitin-associated domains of microtubule-associated protein/microtubule affinity regulating kinase (MARK) 1 and MARK2
J.Biol.Chem., 281:27586-27599, 2006

PubMed Abstract: The microtubule-associated protein (MAP)/microtubule affinity regulating kinase (MARK)/Par-1 phosphorylates microtubule-associated proteins tau, MAP2, and MAP4 and is involved in the regulation of microtubule-based transport. Par-1, a homologue of MARK in Drosophila and Caenorhabditis elegans, is essential for the development of embryonic polarity. Four isoforms of MARK are found in humans. Recently, we reported the crystal structure of the catalytic and ubiquitin-associated domains of MARK2, an isoform enriched in brain (Panneerselvam, S., Marx, A., Mandelkow, E.-M., and Mandelkow, E. (2006) Structure 14, 173-183). It showed that the ubiquitin-associated domain (UBA) domain has an unusual fold and binds to the N-terminal lobe of the catalytic domain. This is at variance with a previous low resolution structure derived from small angle solution scattering (Jaleel, M., Villa, F., Deak, M., Toth, R., Prescott, A. R., Van Aalten, D. M., and Alessi, D. R. (2006) Biochem. J. 394, 545-555), which predicts binding of the UBA domain to the larger, C-terminal lobe. Here we report the crystal structure of the catalytic and UBA domain of another isoform, MARK1. Although the crystal packing of the two isoforms are unrelated, the overall conformations of the molecules are similar. Notably, the UBA domain has the same unusual conformation as in MARK2, and it binds at the same site. Remarkable differences occur in the catalytic domain at helix C, the catalytic loop, and the activation segment.

PubMed: 16803889
DOI: 10.1074/jbc.M604865200

実験手法

X-RAY DIFFRACTION (2.6 Å)