Structural basis for the human SENP5’s SUMO isoform discrimination
Lucía Sánchez-Alba,
Li Ying,
Matthew D. Maletic,
Anna Bolòs,
Helena Borràs-Gas,
Bing Liu,
Nathalia Varejão,
Virginia Amador,
Monique P. C. Mulder and
David Reverter ()
Additional contact information
Lucía Sánchez-Alba: Universitat Autònoma de Barcelona
Li Ying: Universitat Autònoma de Barcelona
Matthew D. Maletic: Leiden University Medical Center (LUMC)
Anna Bolòs: Institut de Investigacions Biomèdiques Agustí Pi i Sunyer (IDIBABS)
Helena Borràs-Gas: Universitat Autònoma de Barcelona
Bing Liu: Universitat Autònoma de Barcelona
Nathalia Varejão: Universitat Autònoma de Barcelona
Virginia Amador: Institut de Investigacions Biomèdiques Agustí Pi i Sunyer (IDIBABS)
Monique P. C. Mulder: Leiden University Medical Center (LUMC)
David Reverter: Universitat Autònoma de Barcelona
Nature Communications, 2025, vol. 16, issue 1, 1-13
Abstract:
Abstract Post-translational SUMO modification is a widespread mechanism for regulating protein function within cells. In humans, SUMO-conjugated proteins are partially regulated by the deconjugating activity of six SENP family members. The proteolytic activity of these enzymes resides within a conserved catalytic domain that exhibits specificity for the two primary SUMO isoforms: SUMO1 and SUMO2/3. SENP5, along with SENP3, are nucleolar proteins involved in ribosome biogenesis and preferentially target SUMO2/3 isoforms. Here, we present the crystal structures of human SENP5 in complex with both SUMO1 and SUMO2 isoforms. These structures reveal a minimal complex interface and elucidate the molecular basis for SENP5’s preference for the SUMO2 isoform. This preference can be attributed to a basic patch surrounding SENP5 Arg624 at the interface. Swapping mutagenesis and structural analysis demonstrate that Arg624 is favorably oriented to interact with Asp63 in SUMO2/3, while its interaction with the equivalent Glu67 in SUMO1 is less favorable. These results suggest that subtle structural differences within SUMO isoforms can significantly influence their deconjugation by SENP enzymes, opening new avenues for exploring the regulation of SUMOylation in various cellular processes and for developing therapeutic agents targeting SUMOylation pathways.
Date: 2025
References: Add references at CitEc
Citations:
Downloads: (external link)
https://www.nature.com/articles/s41467-025-60029-4 Abstract (text/html)
Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.
Export reference: BibTeX
RIS (EndNote, ProCite, RefMan)
HTML/Text
Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60029-4
Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/
DOI: 10.1038/s41467-025-60029-4
Access Statistics for this article
Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie
More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().