4UN0

Crystal structure of the human CDK12-cyclinK complex

「4CJY」から置き換えられました

4UN0 の概要

• エントリーDOI: 10.2210/pdb4un0/pdb
• 分子名称: CYCLIN-K, CYCLIN-DEPENDENT KINASE 12 (2 entities in total)
• 機能のキーワード: transferase
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Nucleus : O75909 Q9NYV4
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 136525.64

構造登録者

Dixon Clarke, S.E.,Elkins, J.M.,Pike, A.C.W.,Chaikuad, A.,Goubin, S.,Krojer, T.,Sorrell, F.J.,Nowak, R.,Williams, E.,Kopec, J.,Mahajan, R.P.,Burgess-Brown, N.,Carpenter, E.P.,Knapp, S.,von Delft, F.,Arrowsmith, C.H.,Edwards, A.M.,Bountra, C.,Bullock, A. (登録日: 2014-05-22, 公開日: 2014-06-04, 最終更新日: 2024-10-16)

主引用文献

Dixon-Clarke, S.E.,Elkins, J.M.,Cheng, S.G.,Morin, G.B.,Bullock, A.N.
Structures of the Cdk12/Cyck Complex with AMP-Pnp Reveal a Flexible C-Terminal Kinase Extension Important for ATP Binding.
Sci.Rep., 5:17122-, 2015

PubMed Abstract: Cyclin-dependent kinase 12 (CDK12) promotes transcriptional elongation by phosphorylation of the RNA polymerase II C-terminal domain (CTD). Structure-function studies show that this activity is dependent on a C-terminal kinase extension, as well as the binding of cyclin K (CycK). To better define these interactions we determined the crystal structure of the human CDK12/CycK complex with and without the kinase extension in the presence of AMP-PNP. The structures revealed novel features for a CDK, including a large β4-β5 loop insertion that contributes to the N-lobe interaction with the cyclin. We also observed two different conformations of the C-terminal kinase extension that effectively open and close the ATP pocket. Most notably, bound AMP-PNP was only observed when trapped in the closed state. Truncation of this C-terminal structure also diminished AMP-PNP binding, as well as the catalytic activity of the CDK12/CycK complex. Further kinetic measurements showed that the full length CDK12/CycK complex was significantly more active than the two crystallised constructs suggesting a critical role for additional domains. Overall, these results demonstrate the intrinsic flexibility of the C-terminal extension in CDK12 and highlight its importance for both ATP binding and kinase activity.

PubMed: 26597175
DOI: 10.1038/SREP17122

実験手法

X-RAY DIFFRACTION (3.15 Å)