Protein degradation by human 20S proteasomes elucidates the interplay between peptide hydrolysis and splicing

Wai Tuck Soh, Hanna P. Roetschke, John A. Cormican, Bei Fang Teo, Nyet Cheng Chiam, Monika Raabe, Ralf Pflanz, Fabian Henneberg, Stefan Becker, Ashwin Chari, Haiyan Liu, Henning Urlaub, Juliane Liepe () and Michele Mishto ()
Additional contact information
Wai Tuck Soh: Max-Planck-Institute for Multidisciplinary Sciences
Hanna P. Roetschke: Max-Planck-Institute for Multidisciplinary Sciences
John A. Cormican: Max-Planck-Institute for Multidisciplinary Sciences
Bei Fang Teo: King’s College London
Nyet Cheng Chiam: Max-Planck-Institute for Multidisciplinary Sciences
Monika Raabe: Max-Planck-Institute for Multidisciplinary Sciences
Ralf Pflanz: Max-Planck-Institute for Multidisciplinary Sciences
Fabian Henneberg: Max-Planck-Institute for Multidisciplinary Sciences
Stefan Becker: Max-Planck-Institute for Multidisciplinary Sciences
Ashwin Chari: Max-Planck-Institute for Multidisciplinary Sciences
Haiyan Liu: National University of Singapore
Henning Urlaub: Max-Planck-Institute for Multidisciplinary Sciences
Juliane Liepe: Max-Planck-Institute for Multidisciplinary Sciences
Michele Mishto: King’s College London

Nature Communications, 2024, vol. 15, issue 1, 1-25

Abstract: Abstract If and how proteasomes catalyze not only peptide hydrolysis but also peptide splicing is an open question that has divided the scientific community. The debate has so far been based on immunopeptidomics, in vitro digestions of synthetic polypeptides as well as ex vivo and in vivo experiments, which could only indirectly describe proteasome-catalyzed peptide splicing of full-length proteins. Here we develop a workflow—and cognate software - to analyze proteasome-generated non-spliced and spliced peptides produced from entire proteins and apply it to in vitro digestions of 15 proteins, including well-known intrinsically disordered proteins such as human tau and α-Synuclein. The results confirm that 20S proteasomes produce a sizeable variety of cis-spliced peptides, whereas trans-spliced peptides are a minority. Both peptide hydrolysis and splicing produce peptides with well-defined characteristics, which hint toward an intricate regulation of both catalytic activities. At protein level, both non-spliced and spliced peptides are not randomly localized within protein sequences, but rather concentrated in hotspots of peptide products, in part driven by protein sequence motifs and proteasomal preferences. At sequence level, the different peptide sequence preference of peptide hydrolysis and peptide splicing suggests a competition between the two catalytic activities of 20S proteasomes during protein degradation.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-45339-3 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:15:y:2024:i:1:d:10.1038_s41467-024-45339-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-45339-3

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 ().