- EMDB-25112: CryoEM map of DNA-PK complex VIIa with AMPPNP -
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基本情報
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データベース: EMDB / ID: EMD-25112
タイトル
CryoEM map of DNA-PK complex VIIa with AMPPNP
マップデータ
試料
複合体: DNA-PK holoenzyme with AMPPNP
機能・相同性
機能・相同性情報
MHC class II antigen presentation / Neutrophil degranulation / entry into host cell by a symbiont-containing vacuole / 加水分解酵素; プロテアーゼ; ペプチド結合加水分解酵素; アスパラギン酸プロテアーゼ / protein autoprocessing / transport vesicle / protein processing / aspartic-type endopeptidase activity / proteolysis 類似検索 - 分子機能
Pepsin-like domain / Eukaryotic aspartyl protease / Aspartic peptidase A1 family / Peptidase family A1 domain / Peptidase family A1 domain profile. / Aspartic peptidase, active site / Eukaryotic and viral aspartyl proteases active site. / Aspartic peptidase domain superfamily 類似検索 - ドメイン・相同性
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)
米国
引用
ジャーナル: Mol Cell / 年: 2022 タイトル: Autophosphorylation transforms DNA-PK from protecting to processing DNA ends. 著者: Lan Liu / Xuemin Chen / Jun Li / Huaibin Wang / Christopher J Buehl / Noah J Goff / Katheryn Meek / Wei Yang / Martin Gellert / 要旨: The DNA-dependent protein kinase (DNA-PK) initially protects broken DNA ends but then promotes their processing during non-homologous end joining (NHEJ). Before ligation by NHEJ, DNA hairpin ends ...The DNA-dependent protein kinase (DNA-PK) initially protects broken DNA ends but then promotes their processing during non-homologous end joining (NHEJ). Before ligation by NHEJ, DNA hairpin ends generated during V(D)J recombination must be opened by the Artemis nuclease, together with autophosphorylated DNA-PK. Structures of DNA-PK bound to DNA before and after phosphorylation, and in complex with Artemis and a DNA hairpin, reveal an essential functional switch. When bound to open DNA ends in its protection mode, DNA-PK is inhibited for cis-autophosphorylation of the so-called ABCDE cluster but activated for phosphorylation of other targets. In contrast, DNA hairpin ends promote cis-autophosphorylation. Phosphorylation of four Thr residues in ABCDE leads to gross structural rearrangement of DNA-PK, widening the DNA binding groove for Artemis recruitment and hairpin cleavage. Meanwhile, Artemis locks DNA-PK into the kinase-inactive state. Kinase activity and autophosphorylation of DNA-PK are regulated by different DNA ends, feeding forward to coordinate NHEJ events.