Cdc48-Ufd1/Npl4 complex processing poly-ubiquitinated substrate in the presence of ADP-BeFx, state 1
マップデータ
Map sharpened with B factor of -150
試料
複合体: Cdc48-Npl4 complex processing poly-ubiquitinated substrate in the presence of ADP-BeFx, state 1
タンパク質・ペプチド: Cell division control protein 48
タンパク質・ペプチド: Nuclear protein localization protein 4
タンパク質・ペプチド: Ubiquitin
リガンド: ADENOSINE-5'-DIPHOSPHATE
リガンド: BERYLLIUM TRIFLUORIDE ION
キーワード
ATPase / ATPase complex / ubiquitin / quality control / MOTOR PROTEIN
機能・相同性
機能・相同性情報
SCF complex disassembly in response to cadmium stress / Ovarian tumor domain proteases / endoplasmic reticulum membrane fusion / Cdc48p-Npl4p-Vms1p AAA ATPase complex / Doa10p ubiquitin ligase complex / DNA replication termination / stress-induced homeostatically regulated protein degradation pathway / sister chromatid biorientation / Hrd1p ubiquitin ligase ERAD-L complex / ribophagy ...SCF complex disassembly in response to cadmium stress / Ovarian tumor domain proteases / endoplasmic reticulum membrane fusion / Cdc48p-Npl4p-Vms1p AAA ATPase complex / Doa10p ubiquitin ligase complex / DNA replication termination / stress-induced homeostatically regulated protein degradation pathway / sister chromatid biorientation / Hrd1p ubiquitin ligase ERAD-L complex / ribophagy / RQC complex / protein localization to vacuole / protein-containing complex disassembly / positive regulation of mitochondrial fusion / cytoplasm protein quality control by the ubiquitin-proteasome system / mitochondria-associated ubiquitin-dependent protein catabolic process / nuclear protein quality control by the ubiquitin-proteasome system / HSF1 activation / protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway / protein phosphatase regulator activity / Translesion Synthesis by POLH / piecemeal microautophagy of the nucleus / mating projection tip / Protein methylation / mitotic spindle disassembly / VCP-NPL4-UFD1 AAA ATPase complex / replisome / vesicle-fusing ATPase / ribosome-associated ubiquitin-dependent protein catabolic process / nonfunctional rRNA decay / retrograde protein transport, ER to cytosol / nuclear outer membrane-endoplasmic reticulum membrane network / KEAP1-NFE2L2 pathway / Neddylation / protein quality control for misfolded or incompletely synthesized proteins / autophagosome maturation / ribosomal large subunit export from nucleus / polyubiquitin modification-dependent protein binding / mRNA transport / ERAD pathway / ATP metabolic process / Neutrophil degranulation / rescue of stalled ribosome / ubiquitin binding / macroautophagy / positive regulation of protein localization to nucleus / modification-dependent protein catabolic process / protein tag activity / ribosome biogenesis / ubiquitin-dependent protein catabolic process / nuclear membrane / proteasome-mediated ubiquitin-dependent protein catabolic process / cytosolic large ribosomal subunit / cytoplasmic translation / protein ubiquitination / structural constituent of ribosome / ubiquitin protein ligase binding / endoplasmic reticulum membrane / perinuclear region of cytoplasm / ATP hydrolysis activity / mitochondrion / ATP binding / identical protein binding / nucleus / cytosol / cytoplasm 類似検索 - 分子機能
NPL4, zinc-binding putative / Nuclear protein localization protein 4 / NPL4 family, putative zinc binding region / Nuclear pore localisation protein NPL4, C-terminal / NPL4 family / AAA ATPase, CDC48 family / Cell division protein 48 (CDC48), N-terminal domain / CDC48, N-terminal subdomain / Cell division protein 48 (CDC48) N-terminal domain / CDC48, domain 2 ...NPL4, zinc-binding putative / Nuclear protein localization protein 4 / NPL4 family, putative zinc binding region / Nuclear pore localisation protein NPL4, C-terminal / NPL4 family / AAA ATPase, CDC48 family / Cell division protein 48 (CDC48), N-terminal domain / CDC48, N-terminal subdomain / Cell division protein 48 (CDC48) N-terminal domain / CDC48, domain 2 / Cell division protein 48 (CDC48), domain 2 / Cell division protein 48 (CDC48) domain 2 / CDC48 domain 2-like superfamily / Aspartate decarboxylase-like domain superfamily / Ribosomal L40e family / Ribosomal_L40e / Ribosomal protein L40e / Ribosomal protein L40e superfamily / AAA ATPase, AAA+ lid domain / AAA+ lid domain / ATPase, AAA-type, conserved site / AAA-protein family signature. / MPN domain / MPN domain profile. / ATPase family associated with various cellular activities (AAA) / : / ATPase, AAA-type, core / Ubiquitin domain signature. / Ubiquitin conserved site / Ubiquitin domain / Ubiquitin family / Ubiquitin homologues / Ubiquitin domain profile. / Ubiquitin-like domain / Ubiquitin-like domain superfamily / ATPases associated with a variety of cellular activities / AAA+ ATPase domain / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性
Ubiquitin-ribosomal protein eL40A fusion protein / Cell division control protein 48 / Nuclear protein localization protein 4 類似検索 - 構成要素
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM052586
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
T32GM007753
米国
引用
ジャーナル: Science / 年: 2019 タイトル: Substrate processing by the Cdc48 ATPase complex is initiated by ubiquitin unfolding. 著者: Edward C Twomey / Zhejian Ji / Thomas E Wales / Nicholas O Bodnar / Scott B Ficarro / Jarrod A Marto / John R Engen / Tom A Rapoport / 要旨: The Cdc48 adenosine triphosphatase (ATPase) (p97 or valosin-containing protein in mammals) and its cofactor Ufd1/Npl4 extract polyubiquitinated proteins from membranes or macromolecular complexes for ...The Cdc48 adenosine triphosphatase (ATPase) (p97 or valosin-containing protein in mammals) and its cofactor Ufd1/Npl4 extract polyubiquitinated proteins from membranes or macromolecular complexes for subsequent degradation by the proteasome. How Cdc48 processes its diverse and often well-folded substrates is unclear. Here, we report cryo-electron microscopy structures of the Cdc48 ATPase in complex with Ufd1/Npl4 and polyubiquitinated substrate. The structures show that the Cdc48 complex initiates substrate processing by unfolding a ubiquitin molecule. The unfolded ubiquitin molecule binds to Npl4 and projects its N-terminal segment through both hexameric ATPase rings. Pore loops of the second ring form a staircase that acts as a conveyer belt to move the polypeptide through the central pore. Inducing the unfolding of ubiquitin allows the Cdc48 ATPase complex to process a broad range of substrates.