futile creatine cycle / creatine kinase / Creatine metabolism / phosphocreatine biosynthetic process / creatine kinase activity / target-directed miRNA degradation / VCB complex / elongin complex / Cul5-RING ubiquitin ligase complex / RND3 GTPase cycle ...futile creatine cycle / creatine kinase / Creatine metabolism / phosphocreatine biosynthetic process / creatine kinase activity / target-directed miRNA degradation / VCB complex / elongin complex / Cul5-RING ubiquitin ligase complex / RND3 GTPase cycle / Cul2-RING ubiquitin ligase complex / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / Tat-mediated elongation of the HIV-1 transcript / ubiquitin-like ligase-substrate adaptor activity / Formation of HIV-1 elongation complex containing HIV-1 Tat / Formation of HIV elongation complex in the absence of HIV Tat / RNA Polymerase II Transcription Elongation / Formation of RNA Pol II elongation complex / RNA Polymerase II Pre-transcription Events / substantia nigra development / transcription corepressor binding / transcription initiation at RNA polymerase II promoter / TP53 Regulates Transcription of DNA Repair Genes / transcription elongation by RNA polymerase II / Vif-mediated degradation of APOBEC3G / Inactivation of CSF3 (G-CSF) signaling / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Evasion by RSV of host interferon responses / Regulation of expression of SLITs and ROBOs / positive regulation of protein catabolic process / Antigen processing: Ubiquitination & Proteasome degradation / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / Neddylation / protein-containing complex assembly / ubiquitin-dependent protein catabolic process / protein-macromolecule adaptor activity / proteasome-mediated ubiquitin-dependent protein catabolic process / protein ubiquitination / intracellular signal transduction / ubiquitin protein ligase binding / regulation of transcription by RNA polymerase II / mitochondrion / extracellular space / extracellular exosome / nucleoplasm / ATP binding / plasma membrane / cytosol 類似検索 - 分子機能
ジャーナル: Nat Commun / 年: 2020 タイトル: Structure and dynamics of the ASB9 CUL-RING E3 Ligase. 著者: Ryan J Lumpkin / Richard W Baker / Andres E Leschziner / Elizabeth A Komives / 要旨: The Cullin 5 (CUL5) Ring E3 ligase uses adaptors Elongins B and C (ELOB/C) to bind different SOCS-box-containing substrate receptors, determining the substrate specificity of the ligase. The 18- ...The Cullin 5 (CUL5) Ring E3 ligase uses adaptors Elongins B and C (ELOB/C) to bind different SOCS-box-containing substrate receptors, determining the substrate specificity of the ligase. The 18-member ankyrin and SOCS box (ASB) family is the largest substrate receptor family. Here we report cryo-EM data for the substrate, creatine kinase (CKB) bound to ASB9-ELOB/C, and for full-length CUL5 bound to the RING protein, RBX2, which binds various E2s. To date, no full structures are available either for a substrate-bound ASB nor for CUL5. Hydrogen-deuterium exchange (HDX-MS) mapped onto a full structural model of the ligase revealed long-range allostery extending from the substrate through CUL5. We propose a revised allosteric mechanism for how CUL-E3 ligases function. ASB9 and CUL5 behave as rigid rods, connected through a hinge provided by ELOB/C transmitting long-range allosteric crosstalk from the substrate through CUL5 to the RBX2 flexible linker.