The proteasomal subunit Rpn6 is a molecular clamp holding the core and regulatory subcomplexes together

Ganesh Ramnath Pathare; István Nagy; Stefan Bohn; Pia Unverdorben; Agnes Hubert; Roman Körner; Stephan Nickell; Keren Lasker; Andrej Sali; Tomohiro Tamura; Taiki Nishioka; Friedrich Förster; Wolfgang Baumeister; Andreas Bracher

doi:10.1073/pnas.1117648108

The proteasomal subunit Rpn6 is a molecular clamp holding the core and regulatory subcomplexes together

Ganesh Ramnath Pathare, István Nagy, Stefan Bohn, Pia Unverdorben, Agnes Hubert, Roman Körner, Stephan Nickell, Keren Lasker, Andrej Sali, Tomohiro Tamura, Taiki Nishioka, Friedrich Förster, Wolfgang Baumeister, Andreas Bracher

extern

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Proteasomes execute the degradation of most cellular proteins. Although the 20S core particle (CP) has been studied in great detail, the structure of the 19S regulatory particle (RP), which prepares ubiquitylated substrates for degradation, has remained elusive. Here, we report the crystal structure of one of the RP subunits, Rpn6, and we describe its integration into the cryo-EM density map of the 26S holocomplex at 9.1 Å resolution. Rpn6 consists of an α-solenoid-like fold and a proteasome COP9/signalosome eIF3 (PCI) module in a right-handed suprahelical configuration. Highly conserved surface areas of Rpn6 interact with the conserved surfaces of the Pre8 (alpha2) and Rpt6 subunits from the alpha and ATPase rings, respectively. The structure suggests that Rpn6 has a pivotal role in stabilizing the otherwise weak interaction between the CP and the RP.

Original language	English
Pages (from-to)	149-54
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	109
Issue number	1
DOIs	https://doi.org/10.1073/pnas.1117648108
Publication status	Published - 3 Jan 2012
Externally published	Yes

Keywords

Amino Acid Sequence
Animals
Conserved Sequence
Crystallography, X-Ray
Drosophila Proteins
Drosophila melanogaster
Models, Molecular
Molecular Sequence Data
Multiprotein Complexes
Proteasome Endopeptidase Complex
Protein Binding
Protein Subunits
Schizosaccharomyces
Solutions
Surface Properties

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10.1073/pnas.1117648108

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Pathare, G. R., Nagy, I., Bohn, S., Unverdorben, P., Hubert, A., Körner, R., Nickell, S., Lasker, K., Sali, A., Tamura, T., Nishioka, T., Förster, F., Baumeister, W., & Bracher, A. (2012). The proteasomal subunit Rpn6 is a molecular clamp holding the core and regulatory subcomplexes together. Proceedings of the National Academy of Sciences of the United States of America, 109(1), 149-54. https://doi.org/10.1073/pnas.1117648108

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title = "The proteasomal subunit Rpn6 is a molecular clamp holding the core and regulatory subcomplexes together",

abstract = "Proteasomes execute the degradation of most cellular proteins. Although the 20S core particle (CP) has been studied in great detail, the structure of the 19S regulatory particle (RP), which prepares ubiquitylated substrates for degradation, has remained elusive. Here, we report the crystal structure of one of the RP subunits, Rpn6, and we describe its integration into the cryo-EM density map of the 26S holocomplex at 9.1 {\AA} resolution. Rpn6 consists of an α-solenoid-like fold and a proteasome COP9/signalosome eIF3 (PCI) module in a right-handed suprahelical configuration. Highly conserved surface areas of Rpn6 interact with the conserved surfaces of the Pre8 (alpha2) and Rpt6 subunits from the alpha and ATPase rings, respectively. The structure suggests that Rpn6 has a pivotal role in stabilizing the otherwise weak interaction between the CP and the RP.",

keywords = "Amino Acid Sequence, Animals, Conserved Sequence, Crystallography, X-Ray, Drosophila Proteins, Drosophila melanogaster, Models, Molecular, Molecular Sequence Data, Multiprotein Complexes, Proteasome Endopeptidase Complex, Protein Binding, Protein Subunits, Schizosaccharomyces, Solutions, Surface Properties",

author = "Pathare, {Ganesh Ramnath} and Istv{\'a}n Nagy and Stefan Bohn and Pia Unverdorben and Agnes Hubert and Roman K{\"o}rner and Stephan Nickell and Keren Lasker and Andrej Sali and Tomohiro Tamura and Taiki Nishioka and Friedrich F{\"o}rster and Wolfgang Baumeister and Andreas Bracher",

year = "2012",

month = jan,

day = "3",

doi = "10.1073/pnas.1117648108",

language = "English",

volume = "109",

pages = "149--54",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences",

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Pathare, GR, Nagy, I, Bohn, S, Unverdorben, P, Hubert, A, Körner, R, Nickell, S, Lasker, K, Sali, A, Tamura, T, Nishioka, T, Förster, F, Baumeister, W & Bracher, A 2012, 'The proteasomal subunit Rpn6 is a molecular clamp holding the core and regulatory subcomplexes together', Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 1, pp. 149-54. https://doi.org/10.1073/pnas.1117648108

The proteasomal subunit Rpn6 is a molecular clamp holding the core and regulatory subcomplexes together. / Pathare, Ganesh Ramnath; Nagy, István; Bohn, Stefan et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, No. 1, 03.01.2012, p. 149-54.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - The proteasomal subunit Rpn6 is a molecular clamp holding the core and regulatory subcomplexes together

AU - Pathare, Ganesh Ramnath

AU - Nagy, István

AU - Bohn, Stefan

AU - Unverdorben, Pia

AU - Hubert, Agnes

AU - Körner, Roman

AU - Nickell, Stephan

AU - Lasker, Keren

AU - Sali, Andrej

AU - Tamura, Tomohiro

AU - Nishioka, Taiki

AU - Förster, Friedrich

AU - Baumeister, Wolfgang

AU - Bracher, Andreas

PY - 2012/1/3

Y1 - 2012/1/3

N2 - Proteasomes execute the degradation of most cellular proteins. Although the 20S core particle (CP) has been studied in great detail, the structure of the 19S regulatory particle (RP), which prepares ubiquitylated substrates for degradation, has remained elusive. Here, we report the crystal structure of one of the RP subunits, Rpn6, and we describe its integration into the cryo-EM density map of the 26S holocomplex at 9.1 Å resolution. Rpn6 consists of an α-solenoid-like fold and a proteasome COP9/signalosome eIF3 (PCI) module in a right-handed suprahelical configuration. Highly conserved surface areas of Rpn6 interact with the conserved surfaces of the Pre8 (alpha2) and Rpt6 subunits from the alpha and ATPase rings, respectively. The structure suggests that Rpn6 has a pivotal role in stabilizing the otherwise weak interaction between the CP and the RP.

AB - Proteasomes execute the degradation of most cellular proteins. Although the 20S core particle (CP) has been studied in great detail, the structure of the 19S regulatory particle (RP), which prepares ubiquitylated substrates for degradation, has remained elusive. Here, we report the crystal structure of one of the RP subunits, Rpn6, and we describe its integration into the cryo-EM density map of the 26S holocomplex at 9.1 Å resolution. Rpn6 consists of an α-solenoid-like fold and a proteasome COP9/signalosome eIF3 (PCI) module in a right-handed suprahelical configuration. Highly conserved surface areas of Rpn6 interact with the conserved surfaces of the Pre8 (alpha2) and Rpt6 subunits from the alpha and ATPase rings, respectively. The structure suggests that Rpn6 has a pivotal role in stabilizing the otherwise weak interaction between the CP and the RP.

KW - Amino Acid Sequence

KW - Animals

KW - Conserved Sequence

KW - Crystallography, X-Ray

KW - Drosophila Proteins

KW - Drosophila melanogaster

KW - Models, Molecular

KW - Molecular Sequence Data

KW - Multiprotein Complexes

KW - Proteasome Endopeptidase Complex

KW - Protein Binding

KW - Protein Subunits

KW - Schizosaccharomyces

KW - Solutions

KW - Surface Properties

U2 - 10.1073/pnas.1117648108

DO - 10.1073/pnas.1117648108

M3 - Article

C2 - 22187461

SN - 0027-8424

VL - 109

SP - 149

EP - 154

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 1

ER -

The proteasomal subunit Rpn6 is a molecular clamp holding the core and regulatory subcomplexes together

Abstract

Keywords

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