Structural basis for the autoinhibition of the C-terminal kinase domain of human RSK1
(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
- Li, Dan ; Fu, Tian Min ; Nan, Jie LU ; Liu, Cong ; Li, Lan Fen and Su, Xiao Dong LU
- publishing date
- 2012-06
- 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
- 2024-09-20 22:33:29
@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}}, }