2019
DOI: 10.1038/s41422-019-0205-0
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Structural insights into the activation of ATM kinase

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Cited by 38 publications
(45 citation statements)
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“…In the apo-ATM and apo-Tel1 structures, both symmetric and asymmetric dimers were observed, with the ATM study suggesting that asymmetry is coupled with an increased basal activity in vitro. A recent study on apo-ATM also presents the existence of ATM monomers in their samples, which are also more active, although it is unclear if these monomers resulted directly from activation (Xiao et al, 2019). Indeed, given the characteristics of the Tel1 dimer interface observed in this study, it seems that a dimer-to-monomer transition would be energetically unfavorable with a free energy of dissociation (DG Diss ) of $37 kcal/mol calculated in PISA (Krissinel and Henrick, 2007).…”
Section: Tel1 Atm Prd-i and Fatc Regulate Substrate Bindingmentioning
confidence: 58%
“…In the apo-ATM and apo-Tel1 structures, both symmetric and asymmetric dimers were observed, with the ATM study suggesting that asymmetry is coupled with an increased basal activity in vitro. A recent study on apo-ATM also presents the existence of ATM monomers in their samples, which are also more active, although it is unclear if these monomers resulted directly from activation (Xiao et al, 2019). Indeed, given the characteristics of the Tel1 dimer interface observed in this study, it seems that a dimer-to-monomer transition would be energetically unfavorable with a free energy of dissociation (DG Diss ) of $37 kcal/mol calculated in PISA (Krissinel and Henrick, 2007).…”
Section: Tel1 Atm Prd-i and Fatc Regulate Substrate Bindingmentioning
confidence: 58%
“…In the last years several ATM structures have been reported, which revealed the overall architecture and enabled assignment of secondary structure, but only allowed building of side-chain models for parts of the protein (Baretic et al, 2017;Lau et al, 2016;Llorca et al, 2003;Sawicka et al, 2016;Wang et al, 2016;Xiao et al, 2019;Xin et al, 2019). ATM is a butterflyshaped dimer, where both protomers interact via the FATKIN domain.…”
Section: Introductionmentioning
confidence: 99%
“…These asymmetric dimers have thus been proposed to represent active conformations or en-route to becoming active. In a more recent cryo-EM study, ATM monomers were detected, albeit at low population [33]. This monomeric population was shown to be more active than dimers [33].…”
Section: Activation Mechanismsmentioning
confidence: 85%
“…In a more recent cryo-EM study, ATM monomers were detected, albeit at low population [33]. This monomeric population was shown to be more active than dimers [33]. While monomerisation could certainly increase kinase activity as many of the inhibitory constraints would be alleviated, it remains to be seen if these monomers result from activation as no monomers were observed in other cryo-EM studies.…”
Section: Activation Mechanismsmentioning
confidence: 89%