7KPV

Structure of kinase and Central lobes of yeast CKM

7KPV の概要

• エントリーDOI: 10.2210/pdb7kpv/pdb
• EMDBエントリー: 22989
• 分子名称: Meiotic mRNA stability protein kinase SSN3, RNA polymerase II holoenzyme cyclin-like subunit, Mediator of RNA polymerase II transcription subunit 12, ... (4 entities in total)
• 機能のキーワード: mediator, transcription, kinase, cdk8, med13, med12, cycc, cdk, argonaute, rna polymerase ii, piwi.
• 由来する生物種: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 428000.47

構造登録者

Li, Y.C.,Chao, T.C.,Kim, H.J.,Cholko, T.,Chen, S.F.,Nakanishi, K.,Chang, C.E.,Murakami, K.,Garcia, B.A.,Boyer, T.G.,Tsai, K.L. (登録日: 2020-11-12, 公開日: 2021-01-27, 最終更新日: 2025-05-14)

主引用文献

Li, Y.C.,Chao, T.C.,Kim, H.J.,Cholko, T.,Chen, S.F.,Li, G.,Snyder, L.,Nakanishi, K.,Chang, C.E.,Murakami, K.,Garcia, B.A.,Boyer, T.G.,Tsai, K.L.
Structure and noncanonical Cdk8 activation mechanism within an Argonaute-containing Mediator kinase module.
Sci Adv, 7:-, 2021

PubMed Abstract: The Cdk8 kinase module (CKM) in Mediator, comprising Med13, Med12, CycC, and Cdk8, regulates RNA polymerase II transcription through kinase-dependent and -independent functions. Numerous pathogenic mutations causative for neurodevelopmental disorders and cancer congregate in CKM subunits. However, the structure of the intact CKM and the mechanism by which Cdk8 is non-canonically activated and functionally affected by oncogenic CKM alterations are poorly understood. Here, we report a cryo-electron microscopy structure of CKM that redefines prior CKM structural models and explains the mechanism of Med12-dependent Cdk8 activation. Med12 interacts extensively with CycC and activates Cdk8 by stabilizing its activation (T-)loop through conserved Med12 residues recurrently mutated in human tumors. Unexpectedly, Med13 has a characteristic Argonaute-like bi-lobal architecture. These findings not only provide a structural basis for understanding CKM function and pathological dysfunction, but also further impute a previously unknown regulatory mechanism of Mediator in transcriptional modulation through its Med13 Argonaute-like features.

PubMed: 33523904
DOI: 10.1126/sciadv.abd4484

実験手法

ELECTRON MICROSCOPY (3.8 Å)