2HAK

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

Summary for 2HAK

• Entry DOI: 10.2210/pdb2hak/pdb
• Related: 1Y8G 1ZMU 1ZMV 1ZMW
• Descriptor: Serine/threonine-protein kinase MARK1 (2 entities in total)
• Functional Keywords: serine/threonine protein kinase; mark; par-1; kin1; uba domain, signaling protein, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane ; Peripheral membrane protein : Q9P0L2
• Total number of polymer chains: 8
• Total formula weight: 301700.03

Authors

Marx, A.,Nugoor, C.,Mueller, J.,Panneerselvam, S.,Mandelkow, E.-M.,Mandelkow, E. (deposition date: 2006-06-13, release date: 2006-07-11, Last modification date: 2023-10-25)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.6 Å)