6SL1

Structure of the open conformation of CtTel1

Summary for 6SL1

• Entry DOI: 10.2210/pdb6sl1/pdb
• EMDB information: 10234
• Descriptor: Serine/threonine-protein kinase Tel1, PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER, MAGNESIUM ION (3 entities in total)
• Functional Keywords: kinase, alpha solenoid, pikk, nucleus, tranferase, dimer, dna damage signaling, transferase
• Biological source: Chaetomium thermophilum (strain DSM 1495 / CBS 144.50 / IMI 039719)
• Total number of polymer chains: 1
• Total formula weight: 330432.55

Authors

Jansma, M.,Eustermann, S.E.,Kostrewa, D.,Lammens, K.,Hopfner, K.P. (deposition date: 2019-08-16, release date: 2019-10-30, Last modification date: 2024-10-16)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.6 Å)