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Molecular and Structural Basis of the Proteasome α Subunit Assembly Mechanism Mediated by the Proteasome-Assembling Chaperone PAC3-PAC4 Heterodimer
Open AccessArticle

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

1
School of Physical Science, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Aichi 444-8787, Japan
2
Institute for Molecular Science, National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan
3
Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan
4
Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan
5
Faculty of Pharmacy, Meijo University, Tempaku-ku, Nagoya 468-8503, Japan
6
National Institute for Physiological Sciences, National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi, 444-8787, Japan
7
Department of Physics, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8602, Japan
8
Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan
9
School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Aichi 444-8787, Japan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(9), 2308; https://doi.org/10.3390/ijms20092308
Received: 27 March 2019 / Revised: 7 May 2019 / Accepted: 7 May 2019 / Published: 9 May 2019
(This article belongs to the Special Issue Designer Biopolymers: Self-Assembling Proteins and Nucleic Acids)
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. View Full-Text
Keywords: proteasome; self-assembly; homo-oligomer; hetero-oligomer; size exclusion chromatography; native mass spectrometry; crystal structure; atomic force microscopy; electron microscopy proteasome; self-assembly; homo-oligomer; hetero-oligomer; size exclusion chromatography; native mass spectrometry; crystal structure; atomic force microscopy; electron microscopy
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Sekiguchi, T.; Satoh, T.; Kurimoto, E.; Song, C.; Kozai, T.; Watanabe, H.; Ishii, K.; Yagi, H.; Yanaka, S.; Uchiyama, S.; Uchihashi, T.; Murata, K.; Kato, K. Mutational and Combinatorial Control of Self-Assembling and Disassembling of Human Proteasome α Subunits. Int. J. Mol. Sci. 2019, 20, 2308.

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