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Structural basis for the autoinhibition of the C-terminal kinase domain of human RSK1

Li, Dan; Fu, Tian Min; Nan, Jie LU ; Liu, Cong; Li, Lan Fen and Su, Xiao Dong LU (2012) In Acta Crystallographica. Section D: Biological Crystallography 68(Pt 6). p.5-680
Abstract

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... (More)

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.

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author
publishing date
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Contribution to journal
publication status
published
keywords
Amino Acid Sequence, Animals, Enzyme Activation, Humans, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Models, Molecular, Molecular Sequence Data, Phosphorylation, Protein Structure, Quaternary, Protein Structure, Tertiary, Ribosomal Protein S6 Kinases, 90-kDa, Sequence Alignment, Substrate Specificity
in
Acta Crystallographica. Section D: Biological Crystallography
volume
68
issue
Pt 6
pages
6 pages
publisher
International Union of Crystallography
external identifiers
  • scopus:84862207771
ISSN
1399-0047
DOI
10.1107/S0907444912007457
language
English
LU publication?
no
id
011eeaf7-d6c5-40af-9f1a-7ce346c4d490
date added to LUP
2016-09-07 22:50:47
date last changed
2017-01-01 08:33:31
@article{011eeaf7-d6c5-40af-9f1a-7ce346c4d490,
  abstract     = {<p>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.</p>},
  author       = {Li, Dan and Fu, Tian Min and Nan, Jie and Liu, Cong and Li, Lan Fen and Su, Xiao Dong},
  issn         = {1399-0047},
  keyword      = {Amino Acid Sequence,Animals,Enzyme Activation,Humans,Mitogen-Activated Protein Kinase 1,Mitogen-Activated Protein Kinase 3,Models, Molecular,Molecular Sequence Data,Phosphorylation,Protein Structure, Quaternary,Protein Structure, Tertiary,Ribosomal Protein S6 Kinases, 90-kDa,Sequence Alignment,Substrate Specificity},
  language     = {eng},
  number       = {Pt 6},
  pages        = {5--680},
  publisher    = {International Union of Crystallography},
  series       = {Acta Crystallographica. Section D: Biological Crystallography},
  title        = {Structural basis for the autoinhibition of the C-terminal kinase domain of human RSK1},
  url          = {http://dx.doi.org/10.1107/S0907444912007457},
  volume       = {68},
  year         = {2012},
}