複合体: UFM1 ribosome E3 ligase complex bound to 60S ribosome
タンパク質・ペプチド: 60S ribosomal protein L10a
タンパク質・ペプチド: E3 UFM1-protein ligase 1
タンパク質・ペプチド: CDK5 regulatory subunit-associated protein 3
タンパク質・ペプチド: DDRGK domain-containing protein 1
タンパク質・ペプチド: Ubiquitin-fold modifier 1
キーワード
UFM1 / Ligase / Ribosome / Complex
機能・相同性
機能・相同性情報
UFM1-modified protein reader activity / UFM1 ligase activity / positive regulation of reticulophagy / regulation of phosphatase activity / apoptotic nuclear changes / definitive erythrocyte differentiation / UFM1 transferase activity / positive regulation of metallopeptidase activity / protein ufmylation / protein K69-linked ufmylation ...UFM1-modified protein reader activity / UFM1 ligase activity / positive regulation of reticulophagy / regulation of phosphatase activity / apoptotic nuclear changes / definitive erythrocyte differentiation / UFM1 transferase activity / positive regulation of metallopeptidase activity / protein ufmylation / protein K69-linked ufmylation / positive regulation of RNA polymerase II regulatory region sequence-specific DNA binding / positive regulation of protein localization to endoplasmic reticulum / negative regulation of protein kinase activity by regulation of protein phosphorylation / positive regulation of plasma cell differentiation / negative regulation of IRE1-mediated unfolded protein response / regulation of proteasomal ubiquitin-dependent protein catabolic process / positive regulation of cell cycle G1/S phase transition / positive regulation of I-kappaB phosphorylation / negative regulation of T cell mediated immune response to tumor cell / protein localization to endoplasmic reticulum / negative regulation of T cell activation / regulation of intracellular estrogen receptor signaling pathway / positive regulation of proteasomal protein catabolic process / negative regulation of protein serine/threonine kinase activity / mitotic G2/M transition checkpoint / ribosome disassembly / 転移酵素; アシル基を移すもの; アミノアシル基を移すもの / cartilage development / regulation of canonical NF-kappaB signal transduction / mitogen-activated protein kinase binding / reticulophagy / regulation of neuron differentiation / response to L-glutamate / negative regulation of NF-kappaB transcription factor activity / regulation of cyclin-dependent protein serine/threonine kinase activity / negative regulation of PERK-mediated unfolded protein response / ubiquitin-like protein ligase binding / regulation of mitotic cell cycle / mitotic G2 DNA damage checkpoint signaling / Peptide chain elongation / positive regulation of glial cell proliferation / Selenocysteine synthesis / positive regulation of signal transduction by p53 class mediator / Formation of a pool of free 40S subunits / Eukaryotic Translation Termination / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / cyclin binding / Viral mRNA Translation / NF-kappaB binding / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / ubiquitin-like ligase-substrate adaptor activity / GTP hydrolysis and joining of the 60S ribosomal subunit / RHOA GTPase cycle / hematopoietic stem cell differentiation / L13a-mediated translational silencing of Ceruloplasmin expression / Major pathway of rRNA processing in the nucleolus and cytosol / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / positive regulation of autophagy / cytosolic ribosome / endoplasmic reticulum unfolded protein response / negative regulation of MAP kinase activity / MDM2/MDM4 family protein binding / negative regulation of proteasomal ubiquitin-dependent protein catabolic process / negative regulation of protein ubiquitination / response to endoplasmic reticulum stress / rescue of stalled ribosome / erythrocyte differentiation / liver development / negative regulation of protein phosphorylation / DNA damage checkpoint signaling / positive regulation of protein ubiquitination / negative regulation of protein catabolic process / regulation of protein stability / brain development / Regulation of expression of SLITs and ROBOs / positive regulation of protein localization to nucleus / osteoblast differentiation / regulation of protein localization / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / Antigen processing: Ubiquitination & Proteasome degradation / regulation of inflammatory response / positive regulation of NF-kappaB transcription factor activity / site of double-strand break / response to ethanol / RNA polymerase II-specific DNA-binding transcription factor binding / cytosolic large ribosomal subunit / mitochondrial outer membrane / cell population proliferation / cytoplasmic translation / postsynaptic density / positive regulation of cell migration / structural constituent of ribosome / translation / neuron projection / negative regulation of gene expression / intracellular membrane-bounded organelle / DNA repair / focal adhesion / centrosome 類似検索 - 分子機能
CDK5 regulatory subunit-associated protein 3 / CDK5 regulatory subunit-associated protein 3 / : / DDRGK domain containing protein / DDRGK domain / DDRGK / E3 UFM1-protein ligase 1 / E3 UFM1-protein ligase 1 / Ubiquitin-fold modifier 1 / Ubiquitin fold modifier 1 protein ...CDK5 regulatory subunit-associated protein 3 / CDK5 regulatory subunit-associated protein 3 / : / DDRGK domain containing protein / DDRGK domain / DDRGK / E3 UFM1-protein ligase 1 / E3 UFM1-protein ligase 1 / Ubiquitin-fold modifier 1 / Ubiquitin fold modifier 1 protein / Ribosomal protein L1, conserved site / Ribosomal protein L1 signature. / Ribosomal protein L1 / Ribosomal protein L1, 3-layer alpha/beta-sandwich / Ribosomal protein L1-like / Ribosomal protein L1/ribosomal biogenesis protein / Ribosomal protein L1p/L10e family / : / Ubiquitin-like domain superfamily / Winged helix DNA-binding domain superfamily / Winged helix-like DNA-binding domain superfamily 類似検索 - ドメイン・相同性
Ubiquitin-fold modifier 1 / E3 UFM1-protein ligase 1 / Large ribosomal subunit protein uL1 / DDRGK domain-containing protein 1 / CDK5 regulatory subunit-associated protein 3 類似検索 - 構成要素
Biotechnology and Biological Sciences Research Council (BBSRC)
BB/T008172/1
英国
European Research Council (ERC)
677623
European Union
Medical Research Council (MRC, United Kingdom)
MC_UU_00018/3
英国
引用
ジャーナル: Nature / 年: 2024 タイトル: The UFM1 E3 ligase recognizes and releases 60S ribosomes from ER translocons. 著者: Linda Makhlouf / Joshua J Peter / Helge M Magnussen / Rohan Thakur / David Millrine / Thomas C Minshull / Grace Harrison / Joby Varghese / Frederic Lamoliatte / Martina Foglizzo / Thomas ...著者: Linda Makhlouf / Joshua J Peter / Helge M Magnussen / Rohan Thakur / David Millrine / Thomas C Minshull / Grace Harrison / Joby Varghese / Frederic Lamoliatte / Martina Foglizzo / Thomas Macartney / Antonio N Calabrese / Elton Zeqiraj / Yogesh Kulathu / 要旨: Stalled ribosomes at the endoplasmic reticulum (ER) are covalently modified with the ubiquitin-like protein UFM1 on the 60S ribosomal subunit protein RPL26 (also known as uL24). This modification, ...Stalled ribosomes at the endoplasmic reticulum (ER) are covalently modified with the ubiquitin-like protein UFM1 on the 60S ribosomal subunit protein RPL26 (also known as uL24). This modification, which is known as UFMylation, is orchestrated by the UFM1 ribosome E3 ligase (UREL) complex, comprising UFL1, UFBP1 and CDK5RAP3 (ref. ). However, the catalytic mechanism of UREL and the functional consequences of UFMylation are unclear. Here we present cryo-electron microscopy structures of UREL bound to 60S ribosomes, revealing the basis of its substrate specificity. UREL wraps around the 60S subunit to form a C-shaped clamp architecture that blocks the tRNA-binding sites at one end, and the peptide exit tunnel at the other. A UFL1 loop inserts into and remodels the peptidyl transferase centre. These features of UREL suggest a crucial function for UFMylation in the release and recycling of stalled or terminated ribosomes from the ER membrane. In the absence of functional UREL, 60S-SEC61 translocon complexes accumulate at the ER membrane, demonstrating that UFMylation is necessary for releasing SEC61 from 60S subunits. Notably, this release is facilitated by a functional switch of UREL from a 'writer' to a 'reader' module that recognizes its product-UFMylated 60S ribosomes. Collectively, we identify a fundamental role for UREL in dissociating 60S subunits from the SEC61 translocon and the basis for UFMylation in regulating protein homeostasis at the ER.