In this section
@article{Yates:2020:10.1016/j.str.2019.10.012,
author = {Yates, L and Williams, R and Hailemariam, S and Ayala, R and Zhang, X},
doi = {10.1016/j.str.2019.10.012},
journal = {Structure},
pages = {96--104.e3},
title = {Cryo-EM structure of nucleotide-bound Tel1ATM unravels the molecular basis of inhibition and structural rationale for disease-associated mutations},
url = {http://dx.doi.org/10.1016/j.str.2019.10.012},
volume = {28},
year = {2020}
}
TY - JOUR
AB - Yeast Tel1 and its highly conserved human orthologue ATM are large protein kinases centralto the maintenance of genome integrity. Mutations in ATM are found in ataxia-telangiectasia(A-T) patients and ATM is one of the most frequently mutated genes in many cancers. Usingcryo electron microscopy, we present the structure of Tel1 in a nucleotide-bound state. Ourstructure reveals molecular details of key residues surrounding the nucleotide binding site andprovides a structural and molecular basis for its intrinsically low basal activity. We show thatthe catalytic residues are in a productive conformation for catalysis, but the PIKK-regulatorydomain-Insert (PRD-I) restricts peptide-substrate access and the N-lobe is in an openconformation, thus explaining the requirement for Tel1 activation. Structural comparisons withother PIKKs suggest a conserved and common allosteric activation mechanism. Our work alsoprovides a structural rationale for many mutations found in A-T and cancer.
AU - Yates,L
AU - Williams,R
AU - Hailemariam,S
AU - Ayala,R
AU - Zhang,X
DO - 10.1016/j.str.2019.10.012
EP - 104
PY - 2020///
SN - 0969-2126
SP - 96
TI - Cryo-EM structure of nucleotide-bound Tel1ATM unravels the molecular basis of inhibition and structural rationale for disease-associated mutations
T2 - Structure
UR - http://dx.doi.org/10.1016/j.str.2019.10.012
UR - http://hdl.handle.net/10044/1/74555
VL - 28
ER -
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