3G51

Structural diversity of the active conformation of the N-terminal kinase domain of p90 ribosomal S6 kinase 2

Summary for 3G51

• Entry DOI: 10.2210/pdb3g51/pdb
• Descriptor: Ribosomal protein S6 kinase alpha-3, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER (3 entities in total)
• Functional Keywords: n-terminal kinase domain of p90 ribosomal s6 kinase 2, atp-binding, kinase, nucleotide-binding, phosphoprotein, serine/threonine-protein kinase, transferase
• Biological source: Mus musculus (mouse)
• Total number of polymer chains: 1
• Total formula weight: 37981.61

Authors

Kurinov, I. (deposition date: 2009-02-04, release date: 2009-12-15, Last modification date: 2023-09-06)

Primary citation

Malakhova, M.,Kurinov, I.,Liu, K.,Zheng, D.,D'Angelo, I.,Shim, J.H.,Steinman, V.,Bode, A.M.,Dong, Z.
Structural diversity of the active N-terminal kinase domain of p90 ribosomal S6 kinase 2
Plos One, 4:e8044-e8044, 2009

PubMed Abstract: The p90 ribosomal protein kinase 2 (RSK2) is a highly expressed Ser/Thr kinase activated by growth factors and is involved in cancer cell proliferation and tumor promoter-induced cell transformation. RSK2 possesses two non-identical kinase domains, and the structure of its N-terminal domain (NTD), which is responsible for phosphorylation of a variety of substrates, is unknown. The crystal structure of the NTD RSK2 was determined at 1.8 A resolution in complex with AMP-PNP. The N-terminal kinase domain adopted a unique active conformation showing a significant structural diversity of the kinase domain compared to other kinases. The NTD RSK2 possesses a three-stranded betaB-sheet inserted in the N-terminal lobe, resulting in displacement of the alphaC-helix and disruption of the Lys-Glu interaction, classifying the kinase conformation as inactive. The purified protein was phosphorylated at Ser227 in the T-activation loop and exhibited in vitro kinase activity. A key characteristic is the appearance of a new contact between Lys216 (betaB-sheet) and the beta-phosphate of AMP-PNP. Mutation of this lysine to alanine impaired both NTDs in vitro and full length RSK2 ex vivo activity, emphasizing the importance of this interaction. Even though the N-terminal lobe undergoes structural re-arrangement, it possesses an intact hydrophobic groove formed between the alphaC-helix, the beta4-strand, and the betaB-sheet junction, which is occupied by the N-terminal tail. The presence of a unique betaB-sheet insert in the N-lobe suggests a different type of activation mechanism for RSK2.

PubMed: 19956600
DOI: 10.1371/journal.pone.0008044

Experimental method

X-RAY DIFFRACTION (1.8 Å)