Item request has been placed! ×
Item request cannot be made. ×
loading  Processing Request

Splicing of distant peptide fragments occurs in the proteasome by transpeptidation and produces the spliced antigenic peptide derived from fibroblast growth factor-5

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
اقرأ أكثر حفظ في قائمتي
  • معلومة اضافية
    • Publisher Information:
      American Association of Immunologists 2010
    • نبذة مختصرة :
      Peptide splicing is a newly described mode of production of antigenic peptides presented by MHC class I molecules, whereby two noncontiguous fragments of the parental protein are joined together after excision of the intervening segment. Three spliced peptides have been described. In two cases, splicing involved the excision of a short intervening segment of 4 or 6 aa and was shown to occur in the proteasome by transpeptidation resulting from the nucleophilic attack of an acyl-enzyme intermediate by the N terminus of the other peptide fragment. For the third peptide, which is derived from fibroblast growth factor-5 (FGF-5), the splicing mechanism remains unknown. In this case, the intervening segment is 40 aa long. This much greater length made the transpeptidation model more difficult to envision. Therefore, we evaluated the role of the proteasome in the splicing of this peptide. We observed that the spliced FGF-5 peptide was produced in vitro after incubation of proteasomes with a 49-aa-long precursor peptide. We evaluated the catalytic mechanism by incubating proteasomes with various precursor peptides. The results confirmed the transpeptidation model of splicing. By transfecting a series of mutant FGF-5 constructs, we observed that reducing the length of the intervening segment increased the production of the spliced peptide, as predicted by the transpeptidation model. Finally, we observed that trans-splicing (i.e., splicing of fragments from two distinct proteins) can occur in the cell, but with a much lower efficacy than splicing of fragments from the same protein.
    • الموضوع:
      Transfection; Protein Splicing; Protein Processing, Post-Translational; Protein Precursors; Proteasome Endopeptidase Complex; Peptide Fragments; Molecular Sequence Data; Humans; Fibroblast Growth Factor 5; Cytotoxicity Tests, Immunologic; Cercopithecus aethiops; Cell Line, Tumor; Cell Line; COS Cells; Antigens; Antigen Presentation; Animals; Amino Acid Sequence; info:eu-repo/semantics/article
    • Availability:
      Open access content. Open access content
      info:eu-repo/semantics/restrictedAccess
    • Note:
      English
    • Other Numbers:
      UCDLC oai:dial.uclouvain.be:boreal:29685
      boreal:29685
      info:doi/10.4049/jimmunol.0901277
      urn:ISSN:0022-1767
      urn:EISSN:1550-6606
      1130573081
    • Contributing Source:
      UNIVERSITE CATHOLIQUE DE LOUVAIN
      From OAIster®, provided by the OCLC Cooperative.
    • الرقم المعرف:
      edsoai.on1130573081
HoldingsOnline