- EMDB-17802: K48-linked ubiquitin chain formation with a cullin-RING E3 ligase... -
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基本情報
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データベース: EMDB / ID: EMD-17802
タイトル
K48-linked ubiquitin chain formation with a cullin-RING E3 ligase and Cdc34: NEDD8-CUL1-RBX1-SKP1-FBXW7 with trapped UBE2R2-donor UB-acceptor UB-cyclin E peptide
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試料
複合体: K48-linked ubiquitin chain formation with a cullin-RING E3 ligase & Cdc34: NEDD8-CUL1-RBX1-SKP1-FBXW7 with trapped UBE2R2~donor UB~acceptor UB-cyclin E peptide
ジャーナル: Nat Struct Mol Biol / 年: 2024 タイトル: Mechanism of millisecond Lys48-linked poly-ubiquitin chain formation by cullin-RING ligases. 著者: Joanna Liwocha / Jerry Li / Nicholas Purser / Chutima Rattanasopa / Samuel Maiwald / David T Krist / Daniel C Scott / Barbara Steigenberger / J Rajan Prabu / Brenda A Schulman / Gary Kleiger / 要旨: E3 ubiquitin ligases, in collaboration with E2 ubiquitin-conjugating enzymes, modify proteins with poly-ubiquitin chains. Cullin-RING ligase (CRL) E3s use Cdc34/UBE2R-family E2s to build Lys48-linked ...E3 ubiquitin ligases, in collaboration with E2 ubiquitin-conjugating enzymes, modify proteins with poly-ubiquitin chains. Cullin-RING ligase (CRL) E3s use Cdc34/UBE2R-family E2s to build Lys48-linked poly-ubiquitin chains to control an enormous swath of eukaryotic biology. Yet the molecular mechanisms underlying this exceptional linkage specificity and millisecond kinetics of poly-ubiquitylation remain unclear. Here we obtain cryogenic-electron microscopy (cryo-EM) structures that provide pertinent insight into how such poly-ubiquitin chains are forged. The CRL RING domain not only activates the E2-bound ubiquitin but also shapes the conformation of a distinctive UBE2R2 loop, positioning both the ubiquitin to be transferred and the substrate-linked acceptor ubiquitin within the active site. The structures also reveal how the ubiquitin-like protein NEDD8 uniquely activates CRLs during chain formation. NEDD8 releases the RING domain from the CRL, but unlike previous CRL-E2 structures, does not contact UBE2R2. These findings suggest how poly-ubiquitylation may be accomplished by many E2s and E3s.
全体 : K48-linked ubiquitin chain formation with a cullin-RING E3 ligase...
全体
名称: K48-linked ubiquitin chain formation with a cullin-RING E3 ligase & Cdc34: NEDD8-CUL1-RBX1-SKP1-FBXW7 with trapped UBE2R2~donor UB~acceptor UB-cyclin E peptide
要素
複合体: K48-linked ubiquitin chain formation with a cullin-RING E3 ligase & Cdc34: NEDD8-CUL1-RBX1-SKP1-FBXW7 with trapped UBE2R2~donor UB~acceptor UB-cyclin E peptide
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超分子 #1: K48-linked ubiquitin chain formation with a cullin-RING E3 ligase...
超分子
名称: K48-linked ubiquitin chain formation with a cullin-RING E3 ligase & Cdc34: NEDD8-CUL1-RBX1-SKP1-FBXW7 with trapped UBE2R2~donor UB~acceptor UB-cyclin E peptide タイプ: complex / ID: 1 / 親要素: 0