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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...

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Autores principales: Li, Shanshan, Hsieh, Kan-Yen, Kuo, Chiao-I, Lee, Szu-Hui, Pintilie, Grigore D., Zhang, Kaiming, Chang, Chung-I
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2021
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.
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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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