دورية أكاديمية

Elucidation of the Signatures of Proteasome-Catalyzed Peptide Splicing

التفاصيل البيبلوغرافية
العنوان: Elucidation of the Signatures of Proteasome-Catalyzed Peptide Splicing
المؤلفون: Paes, Wayne, Leonov, German, Partridge, Thomas, Nicastri, Annalisa, Ternette, Nicola, Borrow, Persephone
المساهمون: National Institutes of Health
المصدر: Frontiers in Immunology ; volume 11 ; ISSN 1664-3224
بيانات النشر: Frontiers Media SA
سنة النشر: 2020
المجموعة: Frontiers (Publisher - via CrossRef)
مصطلحات موضوعية: Immunology, Immunology and Allergy
الوصف: 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.
نوع الوثيقة: article in journal/newspaper
اللغة: unknown
DOI: 10.3389/fimmu.2020.563800
DOI: 10.3389/fimmu.2020.563800/full
الإتاحة: https://doi.org/10.3389/fimmu.2020.563800Test
حقوق: https://creativecommons.org/licenses/by/4.0Test/
رقم الانضمام: edsbas.15465F78
قاعدة البيانات: BASE