Structural basis for the SUMO protease activity of the atypical ubiquitin-specific protease USPL1

Post-translational protein modifications by ubiquitin and ubiquitin-like modifiers regulate many major pathways in the cell. These modifications can be reversed by de-ubiquitinating enzymes such as ubiquitin-specific proteases (USPs). Proteolytic activity towards ubiquitin-modified substrates is com...

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Autores: Li, Ying|||0000-0002-5377-6262, Varejão, Nathalia|||0000-0002-6952-8896, Reverter Cendrós, David|||0000-0002-5347-0992
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:263141
Acceso en línea:https://ddd.uab.cat/record/263141
https://dx.doi.org/urn:doi:10.1038/s41467-022-29485-0
Access Level:acceso abierto
Palabra clave:Protein Binding
Proteolysis
Small Ubiquitin-Related Modifier Proteins
Ubiquitin
Ubiquitin-Specific Proteases
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spelling Structural basis for the SUMO protease activity of the atypical ubiquitin-specific protease USPL1Li, Ying|||0000-0002-5377-6262Varejão, Nathalia|||0000-0002-6952-8896Reverter Cendrós, David|||0000-0002-5347-0992Protein BindingProteolysisSmall Ubiquitin-Related Modifier ProteinsUbiquitinUbiquitin-Specific ProteasesPost-translational protein modifications by ubiquitin and ubiquitin-like modifiers regulate many major pathways in the cell. These modifications can be reversed by de-ubiquitinating enzymes such as ubiquitin-specific proteases (USPs). Proteolytic activity towards ubiquitin-modified substrates is common to all USP family members except for USPL1, which shows a unique preference for the ubiquitin-like modifier SUMO. Here, we present the crystal structure of USPL1 bound to SUMO2, defining the key structural elements for the unusual deSUMOylase activity of USPL1. We identify specific contacts between SUMO2 and the USPL1 subdomains, including a unique hydrogen bond network of the SUMO2 C-terminal tail. In addition, we find that USPL1 lacks major structural elements present in all canonical USPs members such as the so-called blocking loops, which facilitates SUMO binding. Our data give insight into how a structural protein scaffold designed to bind ubiquitin has evolved to bind SUMO, providing an example of divergent evolution in the USP family. 22022-01-0120222022-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/263141https://dx.doi.org/urn:doi:10.1038/s41467-022-29485-0reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengAgencia Estatal de Investigación https://doi.org/10.13039/501100011033 PGC2018-098423-B-I00open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2631412026-06-06T12:50:31Z
dc.title.none.fl_str_mv Structural basis for the SUMO protease activity of the atypical ubiquitin-specific protease USPL1
title Structural basis for the SUMO protease activity of the atypical ubiquitin-specific protease USPL1
spellingShingle Structural basis for the SUMO protease activity of the atypical ubiquitin-specific protease USPL1
Li, Ying|||0000-0002-5377-6262
Protein Binding
Proteolysis
Small Ubiquitin-Related Modifier Proteins
Ubiquitin
Ubiquitin-Specific Proteases
title_short Structural basis for the SUMO protease activity of the atypical ubiquitin-specific protease USPL1
title_full Structural basis for the SUMO protease activity of the atypical ubiquitin-specific protease USPL1
title_fullStr Structural basis for the SUMO protease activity of the atypical ubiquitin-specific protease USPL1
title_full_unstemmed Structural basis for the SUMO protease activity of the atypical ubiquitin-specific protease USPL1
title_sort Structural basis for the SUMO protease activity of the atypical ubiquitin-specific protease USPL1
dc.creator.none.fl_str_mv Li, Ying|||0000-0002-5377-6262
Varejão, Nathalia|||0000-0002-6952-8896
Reverter Cendrós, David|||0000-0002-5347-0992
author Li, Ying|||0000-0002-5377-6262
author_facet Li, Ying|||0000-0002-5377-6262
Varejão, Nathalia|||0000-0002-6952-8896
Reverter Cendrós, David|||0000-0002-5347-0992
author_role author
author2 Varejão, Nathalia|||0000-0002-6952-8896
Reverter Cendrós, David|||0000-0002-5347-0992
author2_role author
author
dc.subject.none.fl_str_mv Protein Binding
Proteolysis
Small Ubiquitin-Related Modifier Proteins
Ubiquitin
Ubiquitin-Specific Proteases
topic Protein Binding
Proteolysis
Small Ubiquitin-Related Modifier Proteins
Ubiquitin
Ubiquitin-Specific Proteases
description Post-translational protein modifications by ubiquitin and ubiquitin-like modifiers regulate many major pathways in the cell. These modifications can be reversed by de-ubiquitinating enzymes such as ubiquitin-specific proteases (USPs). Proteolytic activity towards ubiquitin-modified substrates is common to all USP family members except for USPL1, which shows a unique preference for the ubiquitin-like modifier SUMO. Here, we present the crystal structure of USPL1 bound to SUMO2, defining the key structural elements for the unusual deSUMOylase activity of USPL1. We identify specific contacts between SUMO2 and the USPL1 subdomains, including a unique hydrogen bond network of the SUMO2 C-terminal tail. In addition, we find that USPL1 lacks major structural elements present in all canonical USPs members such as the so-called blocking loops, which facilitates SUMO binding. Our data give insight into how a structural protein scaffold designed to bind ubiquitin has evolved to bind SUMO, providing an example of divergent evolution in the USP family.
publishDate 2022
dc.date.none.fl_str_mv 2
2022-01-01
2022
2022-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/263141
https://dx.doi.org/urn:doi:10.1038/s41467-022-29485-0
url https://ddd.uab.cat/record/263141
https://dx.doi.org/urn:doi:10.1038/s41467-022-29485-0
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PGC2018-098423-B-I00
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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