Solution structure of the kinase-associated domain 1 of mouse microtubule-associated protein/microtubule affinity-regulating kinase 3.
Microtubule-associated protein/microtubule affinity-regulating kinases (MARKs)/PAR-1 are common regulators of cell polarity that are conserved from nematode to human. All of these kinases have a highly conserved C-terminal domain, which is termed the kinase-associated domain 1 (KA1), although its function is unknown. In this study, we determined the solution structure of the KA1 domain of mouse MARK3 by NMR spectroscopy. We found that approximately 50 additional residues preceding the previously defined KA1 domain are required for its proper folding. The newly defined KA1 domain adopts a compact alpha+beta structure with a betaalphabetabetabetabetaalpha topology. We also found a characteristic hydrophobic, concave surface surrounded by positively charged residues. This concave surface includes the highly conserved Glu-Leu-Lys-Leu motif at the C terminus, indicating that it is important for the function of the KA1 domain.
Tochio
Naoya
N
RIKEN Genomic Sciences Center, Tsurumi, Yokohama 230-0045, Japan.
Koshiba
Seizo
S
Kobayashi
Naohiro
N
Inoue
Makoto
M
Yabuki
Takashi
T
Aoki
Masaaki
M
Seki
Eiko
E
Matsuda
Takayoshi
T
Tomo
Yasuko
Y
Motoda
Yoko
Y
Kobayashi
Atsuo
A
Tanaka
Akiko
A
Hayashizaki
Yoshihide
Y
Terada
Takaho
T
Shirouzu
Mikako
M
Kigawa
Takanori
T
Yokoyama
Shigeyuki
S
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D017510:Protein Folding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment / Q000379:methods; D017386:Sequence Homology, Amino Acid; D012997:Solvents; D040681:Structural Homology, Protein
D008869:Microtubule-Associated Proteins; D012997:Solvents; C111833:MARK3 protein, human; D017346:Protein Serine-Threonine Kinases