scholarly journals Mutational and Combinatorial Control of Self-Assembling and Disassembling of Human Proteasome α Subunits

2019 ◽  
Vol 20 (9) ◽  
pp. 2308 ◽  
Author(s):  
Taichiro Sekiguchi ◽  
Tadashi Satoh ◽  
Eiji Kurimoto ◽  
Chihong Song ◽  
Toshiya Kozai ◽  
...  
Keyword(s):  
Ring Structure ◽  
Oligomeric State ◽  
Double Ring ◽  
Self Assembling ◽  
Combinatorial Control ◽  
Α Subunits ◽  
Α7 Subunit

Eukaryotic proteasomes harbor heteroheptameric α-rings, each composed of seven different but homologous subunits α1–α7, which are correctly assembled via interactions with assembly chaperones. The human proteasome α7 subunit is reportedly spontaneously assembled into a homotetradecameric double ring, which can be disassembled into single rings via interaction with monomeric α6. We comprehensively characterized the oligomeric state of human proteasome α subunits and demonstrated that only the α7 subunit exhibits this unique, self-assembling property and that not only α6 but also α4 can disrupt the α7 double ring. We also demonstrated that mutationally monomerized α7 subunits can interact with the intrinsically monomeric α4 and α6 subunits, thereby forming heterotetradecameric complexes with a double-ring structure. The results of this study provide additional insights into the mechanisms underlying the assembly and disassembly of proteasomal subunits, thereby offering clues for the design and creation of circularly assembled hetero-oligomers based on homo-oligomeric structural frameworks.

scholarly journals Structural Fluctuations of the Human Proteasome α7 Homo-Tetradecamer Double Ring Imply the Proteasomal α-Ring Assembly Mechanism

2021 ◽  
Vol 22 (9) ◽  
pp. 4519
Author(s):  
Chihong Song ◽  
Tadashi Satoh ◽  
Taichiro Sekiguchi ◽  
Koichi Kato ◽  
Kazuyoshi Murata
Keyword(s):  
Ring Structure ◽  
20S Proteasome ◽  
Core Complex ◽  
Double Ring ◽  
The Core ◽  
Ring Assembly ◽  
Cryo Electron Microscopy ◽  
Assembly Mechanism ◽  
Structural Fluctuations ◽  
Α Subunits

The 20S proteasome, which is composed of layered α and β heptameric rings, is the core complex of the eukaryotic proteasome involved in proteolysis. The α7 subunit is a component of the α ring, and it self-assembles into a homo-tetradecamer consisting of two layers of α7 heptameric rings. However, the structure of the α7 double ring in solution has not been fully elucidated. We applied cryo-electron microscopy to delineate the structure of the α7 double ring in solution, revealing a structure different from the previously reported crystallographic model. The D7-symmetrical double ring was stacked with a 15° clockwise twist and a separation of 3 Å between the two rings. Two more conformations, dislocated and fully open, were also identified. Our observations suggest that the α7 double-ring structure fluctuates considerably in solution, allowing for the insertion of homologous α subunits, finally converting to the hetero-heptameric α rings in the 20S proteasome.

scholarly journals Toward an understanding of the Cdc48/p97 ATPase

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1318 ◽  
Author(s):  
Nicholas Bodnar ◽  
Tom Rapoport
Keyword(s):  
Atp Hydrolysis ◽  
Critical Role ◽  
Ring Structure ◽  
Cellular Systems ◽  
Aaa Atpase ◽  
Double Ring ◽  
Terminal Domain ◽  
D2 Domain ◽  
Central Pore

A conserved AAA+ ATPase, called Cdc48 in yeast and p97 or VCP in metazoans, plays an essential role in many cellular processes by segregating polyubiquitinated proteins from complexes or membranes. For example, in endoplasmic reticulum (ER)-associated protein degradation (ERAD), Cdc48/p97 pulls polyubiquitinated, misfolded proteins out of the ER and transfers them to the proteasome. Cdc48/p97 consists of an N-terminal domain and two ATPase domains (D1 and D2). Six Cdc48 monomers form a double-ring structure surrounding a central pore. Cdc48/p97 cooperates with a number of different cofactors, which bind either to the N-terminal domain or to the C-terminal tail. The mechanism of Cdc48/p97 action is poorly understood, despite its critical role in many cellular systems. Recent in vitro experiments using yeast Cdc48 and its heterodimeric cofactor Ufd1/Npl4 (UN) have resulted in novel mechanistic insight. After interaction of the substrate-attached polyubiquitin chain with UN, Cdc48 uses ATP hydrolysis in the D2 domain to move the polypeptide through its central pore, thereby unfolding the substrate. ATP hydrolysis in the D1 domain is involved in substrate release from the Cdc48 complex, which requires the cooperation of the ATPase with a deubiquitinase (DUB). Surprisingly, the DUB does not completely remove all ubiquitin molecules; the remaining oligoubiquitin chain is also translocated through the pore. Cdc48 action bears similarities to the translocation mechanisms employed by bacterial AAA ATPases and the eukaryotic 19S subunit of the proteasome, but differs significantly from that of a related type II ATPase, the NEM-sensitive fusion protein (NSF). Many questions about Cdc48/p97 remain unanswered, including how it handles well-folded substrate proteins, how it passes substrates to the proteasome, and how various cofactors modify substrates and regulate its function.

Body-Insensitive Multimode MIMO Terminal Antenna of Double-Ring Structure

2015 ◽  
Vol 63 (5) ◽  
pp. 1925-1936 ◽  
Author(s):  
Kun Zhao ◽  
Shuai Zhang ◽  
Katsunori Ishimiya ◽  
Zhinong Ying ◽  
Sailing He
Keyword(s):  
Ring Structure ◽  
Double Ring
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