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Complete three-dimensional structures of the Lon protease translocating a protein substrate
Lon is an evolutionarily conserved proteolytic machine carrying out a wide spectrum of biological activities by degrading misfolded damaged proteins and specific cellular substrates. Lon contains a large N-terminal domain and forms a hexameric core of fused adenosine triphosphatase and protease doma...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8519571/ https://www.ncbi.nlm.nih.gov/pubmed/34652947 http://dx.doi.org/10.1126/sciadv.abj7835 |
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author | Li, Shanshan Hsieh, Kan-Yen Kuo, Chiao-I Lee, Szu-Hui Pintilie, Grigore D. Zhang, Kaiming Chang, Chung-I |
author_facet | Li, Shanshan Hsieh, Kan-Yen Kuo, Chiao-I Lee, Szu-Hui Pintilie, Grigore D. Zhang, Kaiming Chang, Chung-I |
author_sort | Li, Shanshan |
collection | PubMed |
description | Lon is an evolutionarily conserved proteolytic machine carrying out a wide spectrum of biological activities by degrading misfolded damaged proteins and specific cellular substrates. Lon contains a large N-terminal domain and forms a hexameric core of fused adenosine triphosphatase and protease domains. Here, we report two complete structures of Lon engaging a substrate, determined by cryo–electron microscopy to 2.4-angstrom resolution. These structures show a multilayered architecture featuring a tensegrity triangle complex, uniquely constructed by six long N-terminal helices. The interlocked helix triangle is assembled on the top of the hexameric core to spread a web of six globular substrate-binding domains. It serves as a multipurpose platform that controls the access of substrates to the AAA+ ring, provides a ruler-based mechanism for substrate selection, and acts as a pulley device to facilitate unfolding of the translocated substrate. This work provides a complete framework for understanding the structural mechanisms of Lon. |
format | Online Article Text |
id | pubmed-8519571 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-85195712021-10-26 Complete three-dimensional structures of the Lon protease translocating a protein substrate Li, Shanshan Hsieh, Kan-Yen Kuo, Chiao-I Lee, Szu-Hui Pintilie, Grigore D. Zhang, Kaiming Chang, Chung-I Sci Adv Biomedicine and Life Sciences Lon is an evolutionarily conserved proteolytic machine carrying out a wide spectrum of biological activities by degrading misfolded damaged proteins and specific cellular substrates. Lon contains a large N-terminal domain and forms a hexameric core of fused adenosine triphosphatase and protease domains. Here, we report two complete structures of Lon engaging a substrate, determined by cryo–electron microscopy to 2.4-angstrom resolution. These structures show a multilayered architecture featuring a tensegrity triangle complex, uniquely constructed by six long N-terminal helices. The interlocked helix triangle is assembled on the top of the hexameric core to spread a web of six globular substrate-binding domains. It serves as a multipurpose platform that controls the access of substrates to the AAA+ ring, provides a ruler-based mechanism for substrate selection, and acts as a pulley device to facilitate unfolding of the translocated substrate. This work provides a complete framework for understanding the structural mechanisms of Lon. American Association for the Advancement of Science 2021-10-15 /pmc/articles/PMC8519571/ /pubmed/34652947 http://dx.doi.org/10.1126/sciadv.abj7835 Text en Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Li, Shanshan Hsieh, Kan-Yen Kuo, Chiao-I Lee, Szu-Hui Pintilie, Grigore D. Zhang, Kaiming Chang, Chung-I Complete three-dimensional structures of the Lon protease translocating a protein substrate |
title | Complete three-dimensional structures of the Lon protease translocating a protein substrate |
title_full | Complete three-dimensional structures of the Lon protease translocating a protein substrate |
title_fullStr | Complete three-dimensional structures of the Lon protease translocating a protein substrate |
title_full_unstemmed | Complete three-dimensional structures of the Lon protease translocating a protein substrate |
title_short | Complete three-dimensional structures of the Lon protease translocating a protein substrate |
title_sort | complete three-dimensional structures of the lon protease translocating a protein substrate |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8519571/ https://www.ncbi.nlm.nih.gov/pubmed/34652947 http://dx.doi.org/10.1126/sciadv.abj7835 |
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