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Lysine acetylation: a new protein modification in PPAR‐alpha agonist induced peroxisomes
Author(s) -
Contreras Miguel A.,
Baatz John E.,
Singh Inderjit
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1026.10
Subject(s) - peroxisome , biochemistry , peroxisomal targeting signal , organelle , acetylation , lysine , biology , in silico , chemistry , receptor , amino acid , gene
Peroxisomes are ubiquitous subcellular organelles that play important role in cellular metabolisms and related disease processes. To date, very few of the peroxisomal proteins have been reported to be posttranslational modified. In this study we screen PPARα‐induced peroxisomal proteins for the presence of acetyl‐modifications. Subcellular organelle proteins from a rat liver peroxisomes‐enriched fraction separated by a linear density gradient were analyzed by Western blot using acetylated‐lysine‐specific antibody. A single 80kDa band was identified in an area where the peroxisomal enzymatic marker catalase localized. LC‐MS/MS analysis of the bands excised from SDS‐PAGE and from 2D resolved immunoprecipitated proteins were then used to identify peptides chemically modified. A peptide containing acetylated lysine having the sequence ( 69 avanydsgeage k 81 ) was identified and consistent with the peroxisomal multifunctional enzyme‐2 (MFE‐2) protein sequence. In silico analyses for acetyl‐modification of MFE‐2 sequence supported our finding. Analysis of MFE‐2 tertiary protein structure resulted in mapping the modified residue ( 81 Lys) to the MFE‐2 surface, specifically on the (3R)‐hydroxyacyl‐CoA dehydrogenase domain. In summary, this is the first report of acetyl‐modification of a protein in PPARα‐induced peroxisomes. (Supported by NIH grant NS‐34741 and NCRR grants C06 RR018823 and C06 RR015455).