6SL0

Complete CtTel1 dimer with C2 symmetry

6SL0 の概要

• エントリーDOI: 10.2210/pdb6sl0/pdb
• EMDBエントリー: 10233
• 分子名称: Serine/threonine-protein kinase Tel1, PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER, MAGNESIUM ION (3 entities in total)
• 機能のキーワード: kinase, alpha solenoid, pikk, nucleus, tranferase, dimer, dna damage signaling, transferase
• 由来する生物種: Chaetomium thermophilum (strain DSM 1495 / CBS 144.50 / IMI 039719)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 660949.17

構造登録者

Jansma, M.,Eustermann, S.E.,Kostrewa, D.,Lammens, K.,Hopfner, K.P. (登録日: 2019-08-16, 公開日: 2019-10-30, 最終更新日: 2024-10-23)

主引用文献

Jansma, M.,Linke-Winnebeck, C.,Eustermann, S.,Lammens, K.,Kostrewa, D.,Stakyte, K.,Litz, C.,Kessler, B.,Hopfner, K.P.
Near-Complete Structure and Model of Tel1ATM from Chaetomium thermophilum Reveals a Robust Autoinhibited ATP State.
Structure, 28:83-95.e5, 2020

PubMed Abstract: 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.

PubMed: 31740028
DOI: 10.1016/j.str.2019.10.013

実験手法

ELECTRON MICROSCOPY (3.7 Å)