Document Detail


Site-specific methionine sulfoxide formation is the structural basis of chromatographic heterogeneity of apolipoproteins A-I, C-II, and C-III.
MedLine Citation:
PMID:  1753217     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
ApoA-I and apoC-II are eluted in two isoforms and apoC-III2 is eluted in three isoforms by reversed phase high performance liquid chromatography (HPLC). The structural basis of these nongenetic heterogeneities was unravelled using HPLC of proteolytic peptides and time-of-flight secondary ion mass spectrometry (TOF-SIMS). In apoA-I, the chromatographic microheterogeneity was caused by the formation of methionine sulfoxides (MetSO). However, only residues Met112 and Met148 were found oxidized, whereas Met86 was unaffected and also resistant towards artificial oxidation. To assess whether and to what extent amino acid substitutions in apoA-I might affect methionine sulfoxidation, the tryptic peptides of 13 different mutant apoA-I proteins from 24 heterozygous apoA-I variant carriers were analyzed by HPLC. In normal apoA-I, the ratios MetSO112/Met112 and MetSO148/Met148 were highly variable. By contrast, the relative ratio of oxidation of methionine residues 112 and 148 was constant. The amino acid changes Lys107----Met, Lys107----O, Glu139----Gly, Glu147----Val, and Pro165----Arg resulted in the preferential oxidation of Met112, and Asp103----Asn resulted in a preferential oxidation of Met148; whereas Pro3----Arg, Pro3----His, Pro4----Arg, Asp89----Glu, Ala158----Asp, Glu198----Lys, and Asp213----Gly had no impact. ApoC-II and apoC-III isoforms differed by the oxidation of the two methionine residues in these proteins. Whereas in apoC-II both methionine residues were oxidized in parallel, in apoC-III the two methionine residues differed in their susceptibility towards oxidation. We conclude that the formation of MetSO depends on the molecular microenvironment within a protein.
Authors:
A von Eckardstein; M Walter; H Holz; A Benninghoven; G Assmann
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of lipid research     Volume:  32     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  1991 Sep 
Date Detail:
Created Date:  1992-01-24     Completed Date:  1992-01-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1465-76     Citation Subset:  IM    
Affiliation:
Institut für Klinische Chemie und Laboratoriumsmedizin, Westfälische Wilhelms-Universität Münster, Germany.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Apolipoprotein A-I / chemistry,  genetics,  isolation & purification*
Apolipoprotein C-II
Apolipoprotein C-III
Apolipoproteins C / chemistry,  genetics,  isolation & purification*
Chromatography, High Pressure Liquid
Humans
Mass Spectrometry
Methionine / analogs & derivatives
Molecular Sequence Data
Molecular Structure
Mutation
Oxidation-Reduction
Peptide Fragments / chemistry,  isolation & purification
Chemical
Reg. No./Substance:
0/Apolipoprotein A-I; 0/Apolipoprotein C-II; 0/Apolipoprotein C-III; 0/Apolipoproteins C; 0/Peptide Fragments; 454-41-1/methionine sulfoxide; 63-68-3/Methionine

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