Structural basis for the autoinhibition of the C-terminal kinase domain of human RSK1.
p90 ribosomal S6 kinases (RSKs) respond to various mitogen stimuli and comprise two distinct protein kinase domains. The C-terminal kinase domain (CTKD) receives signal from ERK1/2 and adopts an autoinhibitory mechanism. Here, the crystal structure of human RSK1 CTKD is reported at 2.7 Å resolution. The structure shows a standard kinase fold, with the catalytic residues in the ATP-binding cleft orientated in optimal conformations for phosphotransfer. The inactivation of the CTKD is conferred by an extra α-helix (αL), which occupies the substrate-binding groove. In combination with previous knowledge, this structure indicates that activation of RSK1 involves the removal of αL from the substrate-binding groove induced by ERK1/2 phosphorylation.
State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, People's Republic of China.
Dan
D
Li
Tian Min
TM
Fu
Jie
J
Nan
Cong
C
Liu
Lan Fen
LF
Li
Xiao Dong
XD
Su
D000595:Amino Acid Sequence; D000818:Animals; D004789:Enzyme Activation; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010766:Phosphorylation; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000737:chemistry* / Q000378:metabolism; D016415:Sequence Alignment; D013379:Substrate Specificity
D038744:Ribosomal Protein S6 Kinases, 90-kDa; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3