PMID- 33072102
OWN - NLM
STAT- MEDLINE
DCOM- 20210503
LR  - 20220323
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 11
DP  - 2020
TI  - Elucidation of the Signatures of Proteasome-Catalyzed Peptide Splicing.
PG  - 563800
LID - 10.3389/fimmu.2020.563800 [doi]
LID - 563800
AB  - 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(+) 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.
CI  - Copyright (c) 2020 Paes, Leonov, Partridge, Nicastri, Ternette and Borrow.
FAU - Paes, Wayne
AU  - Paes W
AD  - Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United 
      Kingdom.
FAU - Leonov, German
AU  - Leonov G
AD  - York Cross-Disciplinary Center for Systems Analysis, University of York, York, 
      United Kingdom.
FAU - Partridge, Thomas
AU  - Partridge T
AD  - Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United 
      Kingdom.
FAU - Nicastri, Annalisa
AU  - Nicastri A
AD  - Nuffield Department of Clinical Medicine, The Jenner Institute, University of 
      Oxford, Oxford, United Kingdom.
FAU - Ternette, Nicola
AU  - Ternette N
AD  - Nuffield Department of Clinical Medicine, The Jenner Institute, University of 
      Oxford, Oxford, United Kingdom.
FAU - Borrow, Persephone
AU  - Borrow P
AD  - Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United 
      Kingdom.
LA  - eng
GR  - MR/K012037/1/MRC_/Medical Research Council/United Kingdom
GR  - R01 AI118549/AI/NIAID NIH HHS/United States
GR  - UM1 AI100645/AI/NIAID NIH HHS/United States
GR  - MR/K012037/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200924
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Peptide Fragments)
RN  - 0 (Peptides)
RN  - 0 (Viral Proteins)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
EIN - Front Immunol. 2021 Sep 23;12:755002. PMID: 34630434
MH  - Amino Acid Sequence
MH  - Antigen Presentation
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Catalysis
MH  - Catalytic Domain
MH  - Chemistry Techniques, Synthetic
MH  - Chromatography, Liquid
MH  - Computer Simulation
MH  - Epitopes, T-Lymphocyte/chemistry/immunology
MH  - HIV-1/*chemistry
MH  - Histocompatibility Antigens Class I/immunology
MH  - Humans
MH  - Peptide Fragments/chemistry
MH  - Peptides/*chemistry
MH  - Proteasome Endopeptidase Complex/*chemistry
MH  - *Protein Splicing
MH  - Proteolysis
MH  - Tandem Mass Spectrometry
MH  - Viral Proteins/*chemistry
PMC - PMC7541919
OTO - NOTNLM
OT  - antigen processing
OT  - peptide epitopes
OT  - peptide splicing
OT  - proteasome
OT  - splicing mechanism
EDAT- 2020/10/20 06:00
MHDA- 2021/05/04 06:00
PMCR- 2020/01/01
CRDT- 2020/10/19 05:56
PHST- 2020/05/19 00:00 [received]
PHST- 2020/08/26 00:00 [accepted]
PHST- 2020/10/19 05:56 [entrez]
PHST- 2020/10/20 06:00 [pubmed]
PHST- 2021/05/04 06:00 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2020.563800 [doi]
PST - epublish
SO  - Front Immunol. 2020 Sep 24;11:563800. doi: 10.3389/fimmu.2020.563800. eCollection 
      2020.