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Elucidation of the Signatures of Proteasome-Catalyzed Peptide Splicing.
- Source :
-
Frontiers in immunology [Front Immunol] 2020 Sep 24; Vol. 11, pp. 563800. Date of Electronic Publication: 2020 Sep 24 (Print Publication: 2020). - Publication Year :
- 2020
-
Abstract
- Proteasomes catalyze the degradation of endogenous proteins into oligopeptides, but can concurrently create spliced oligopeptides through ligation of previously non-contiguous peptide fragments. Recent studies have uncovered a formerly unappreciated role for proteasome-catalyzed peptide splicing (PCPS) in the generation of non-genomically templated human leukocyte antigen class I (HLA-I)-bound cis- spliced peptides that can be targeted by CD8 <superscript>+</superscript> T cells in cancer and infection. However, the mechanisms defining PCPS reactions are poorly understood. Here, we experimentally define the biochemical constraints of proteasome-catalyzed cis -splicing reactions by examination of in vitro proteasomal digests of a panel of viral- and self-derived polypeptide substrates using a tailored mass-spectrometry-based de novo sequencing workflow. We show that forward and reverse PCPS reactions display unique splicing signatures, defined by preferential fusion of distinct amino acid residues with stringent peptide length distributions, suggesting sequence- and size-dependent accessibility of splice reactants for proteasomal substrate binding pockets. Our data provide the basis for a more informed mechanistic understanding of PCPS that will facilitate future prediction of spliced peptides from protein sequences.<br /> (Copyright © 2020 Paes, Leonov, Partridge, Nicastri, Ternette and Borrow.)
- Subjects :
- Amino Acid Sequence
Antigen Presentation
CD8-Positive T-Lymphocytes immunology
Catalysis
Catalytic Domain
Chemistry Techniques, Synthetic
Chromatography, Liquid
Computer Simulation
Epitopes, T-Lymphocyte chemistry
Epitopes, T-Lymphocyte immunology
Histocompatibility Antigens Class I immunology
Humans
Peptide Fragments chemistry
Proteolysis
Tandem Mass Spectrometry
HIV-1 chemistry
Peptides chemistry
Proteasome Endopeptidase Complex chemistry
Protein Splicing
Viral Proteins chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 11
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 33072102
- Full Text :
- https://doi.org/10.3389/fimmu.2020.563800