Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; and
publishing date
type
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
John Wiley & Sons Inc.
external identifiers
  • pmid:22683790
  • 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
2024-01-04 12:04:35
@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}},
  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}},
  language     = {{eng}},
  number       = {{Pt 6}},
  pages        = {{5--680}},
  publisher    = {{John Wiley & Sons Inc.}},
  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}},
  doi          = {{10.1107/S0907444912007457}},
  volume       = {{68}},
  year         = {{2012}},
}