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A Role for the Proteasome Alpha2 Subunit N-Tail in Substrate Processing
The proteolytic active sites of the 26S proteasome are sequestered within the catalytic chamber of its 20S core particle (CP). Access to this chamber is through a narrow channel defined by the seven outer α subunits. In the resting state, the N-termini of neighboring α subunits form a gate blocking...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10046698/ https://www.ncbi.nlm.nih.gov/pubmed/36979414 http://dx.doi.org/10.3390/biom13030480 |
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author | Sahu, Indrajit Bajorek, Monika Tan, Xiaolin Srividya, Madabhushi Krutauz, Daria Reis, Noa Osmulski, Pawel A. Gaczynska, Maria E. Glickman, Michael H. |
author_facet | Sahu, Indrajit Bajorek, Monika Tan, Xiaolin Srividya, Madabhushi Krutauz, Daria Reis, Noa Osmulski, Pawel A. Gaczynska, Maria E. Glickman, Michael H. |
author_sort | Sahu, Indrajit |
collection | PubMed |
description | The proteolytic active sites of the 26S proteasome are sequestered within the catalytic chamber of its 20S core particle (CP). Access to this chamber is through a narrow channel defined by the seven outer α subunits. In the resting state, the N-termini of neighboring α subunits form a gate blocking access to the channel. The attachment of the activators or regulatory particles rearranges the blocking α subunit N-termini facilitating the entry of substrates. By truncating or mutating each of the participating α N-termini, we report that whereas only a few N-termini are important for maintaining the closed gate, all seven N-termini participate in the open gate. Specifically, the open state is stabilized by a hydrogen bond between an invariant tyrosine (Y) in each subunit with a conserved aspartate (D) in its counterclockwise neighbor. The lone exception is the α1–α2 pair leaving a gap in the ring circumference. The third residue (X) of this YD(X) motif aligns with the open channel. Phenylalanine at this position in the α2 subunit comes in direct contact with the translocating substrate. Consequently, deletion of the α2 N-terminal tail attenuates proteolysis despite the appearance of an open gate state. In summary, the interlacing N-terminal YD(X) motifs regulate both the gating and translocation of the substrate. |
format | Online Article Text |
id | pubmed-10046698 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100466982023-03-29 A Role for the Proteasome Alpha2 Subunit N-Tail in Substrate Processing Sahu, Indrajit Bajorek, Monika Tan, Xiaolin Srividya, Madabhushi Krutauz, Daria Reis, Noa Osmulski, Pawel A. Gaczynska, Maria E. Glickman, Michael H. Biomolecules Article The proteolytic active sites of the 26S proteasome are sequestered within the catalytic chamber of its 20S core particle (CP). Access to this chamber is through a narrow channel defined by the seven outer α subunits. In the resting state, the N-termini of neighboring α subunits form a gate blocking access to the channel. The attachment of the activators or regulatory particles rearranges the blocking α subunit N-termini facilitating the entry of substrates. By truncating or mutating each of the participating α N-termini, we report that whereas only a few N-termini are important for maintaining the closed gate, all seven N-termini participate in the open gate. Specifically, the open state is stabilized by a hydrogen bond between an invariant tyrosine (Y) in each subunit with a conserved aspartate (D) in its counterclockwise neighbor. The lone exception is the α1–α2 pair leaving a gap in the ring circumference. The third residue (X) of this YD(X) motif aligns with the open channel. Phenylalanine at this position in the α2 subunit comes in direct contact with the translocating substrate. Consequently, deletion of the α2 N-terminal tail attenuates proteolysis despite the appearance of an open gate state. In summary, the interlacing N-terminal YD(X) motifs regulate both the gating and translocation of the substrate. MDPI 2023-03-05 /pmc/articles/PMC10046698/ /pubmed/36979414 http://dx.doi.org/10.3390/biom13030480 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sahu, Indrajit Bajorek, Monika Tan, Xiaolin Srividya, Madabhushi Krutauz, Daria Reis, Noa Osmulski, Pawel A. Gaczynska, Maria E. Glickman, Michael H. A Role for the Proteasome Alpha2 Subunit N-Tail in Substrate Processing |
title | A Role for the Proteasome Alpha2 Subunit N-Tail in Substrate Processing |
title_full | A Role for the Proteasome Alpha2 Subunit N-Tail in Substrate Processing |
title_fullStr | A Role for the Proteasome Alpha2 Subunit N-Tail in Substrate Processing |
title_full_unstemmed | A Role for the Proteasome Alpha2 Subunit N-Tail in Substrate Processing |
title_short | A Role for the Proteasome Alpha2 Subunit N-Tail in Substrate Processing |
title_sort | role for the proteasome alpha2 subunit n-tail in substrate processing |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10046698/ https://www.ncbi.nlm.nih.gov/pubmed/36979414 http://dx.doi.org/10.3390/biom13030480 |
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