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-Structure paper
タイトル | Near-Complete Structure and Model of Tel1ATM from Chaetomium thermophilum Reveals a Robust Autoinhibited ATP State. |
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ジャーナル・号・ページ | Structure, Vol. 28, Issue 1, Page 83-95.e5, Year 2020 |
掲載日 | 2020年1月7日 |
著者 | Marijke Jansma / Christian Linke-Winnebeck / Sebastian Eustermann / Katja Lammens / Dirk Kostrewa / Kristina Stakyte / Claudia Litz / Brigitte Kessler / Karl-Peter Hopfner / |
PubMed 要旨 | Tel1 (ATM in humans) is a large kinase that resides in the cell in an autoinhibited dimeric state and upon activation orchestrates the cellular response to DNA damage. We report the structure of an ...Tel1 (ATM in humans) is a large kinase that resides in the cell in an autoinhibited dimeric state and upon activation orchestrates the cellular response to DNA damage. We report the structure of an endogenous Tel1 dimer from Chaetomium thermophilum. Major parts are at 2.8 Å resolution, including the kinase active site with ATPγS bound, and two different N-terminal solenoid conformations are at 3.4 Å and 3.6 Å, providing a side-chain model for 90% of the Tel1 polypeptide. We show that the N-terminal solenoid has DNA binding activity, but that its movements are not coupled to kinase activation. Although ATPγS and catalytic residues are poised for catalysis, the kinase resides in an autoinhibited state. The PIKK regulatory domain acts as a pseudo-substrate, blocking direct access to the site of catalysis. The structure allows mapping of human cancer mutations and defines mechanisms of autoinhibition at near-atomic resolution. |
リンク | Structure / PubMed:31740028 |
手法 | EM (単粒子) |
解像度 | 2.8 - 3.7 Å |
構造データ | EMDB-10231, PDB-6sky: EMDB-10232, PDB-6skz: EMDB-10233, PDB-6sl0: EMDB-10234, PDB-6sl1: |
化合物 | ChemComp-AGS: ChemComp-MG: |
由来 |
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キーワード | TRANSFERASE / Kinase / alpha solenoid / PIKK / nucleus / tranferase / dimer / DNA damage signaling / ATM |