Journal of Lipid Research, Vol 32, 1465-1476, Copyright © 1991 by Lipid Research, Inc.

ARTICLES

Site-specific methionine sulfoxide formation is the structural basis of chromatographic heterogeneity of apolipoproteins A-I, C-II, and C-III

A von Eckardstein, M Walter, H Holz, A Benninghoven and G Assmann
Institut fur Klinische Chemie und Laboratoriumsmedizin, Westfalische Wilhelms-Universitat Munster, Germany.

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.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. W. C. Brock, A. J. Jenkins, T. J. Lyons, R. L. Klein, E. Yim, M. Lopes-Virella, R. E. Carter, (DCCT/EDIC) Research Group, S. R. Thorpe, and J. W. Baynes Increased methionine sulfoxide content of apoA-I in type 1 diabetes J. Lipid Res., April 1, 2008; 49(4): 847 - 855. [Abstract] [Full Text] [PDF]

				T. Sako, E. Uchida, Y. Kagawa, K. Hirayama, T. Nakade, and H. Taniyama Immunohistochemical Detection of Apolipoprotein A-I and B-100 in Canine Atherosclerotic Lesions Vet. Pathol., May 1, 2003; 40(3): 328 - 331. [Abstract] [Full Text] [PDF]

				G. Pankhurst, X. L. Wang, D. E. Wilcken, G. Baernthaler, U. Panzenbock, M. Raftery, and R. Stocker Characterization of specifically oxidized apolipoproteins in mildly oxidized high density lipoprotein J. Lipid Res., February 1, 2003; 44(2): 349 - 355. [Abstract] [Full Text] [PDF]

				P. V. Bondarenko, S. L. Cockrill, L. K. Watkins, I. D. Cruzado, and R. D. Macfarlane Mass spectral study of polymorphism of the apolipoproteins of very low density lipoprotein J. Lipid Res., March 1, 1999; 40(3): 543 - 555. [Abstract] [Full Text]

				R. Mashima, Y. Yamamoto, and S. Yoshimura Reduction of phosphatidylcholine hydroperoxide by apolipoprotein A-I: purification of the hydroperoxide-reducing proteins from human blood plasma J. Lipid Res., June 1, 1998; 39(6): 1133 - 1140. [Abstract] [Full Text]

				A. von Eckardstein, A. Chirazi, S. Schuler-Lüttmann, M. Walter, J. J. P. Kastelein, J. Geisel, J. T. Real, R. Miccoli, G. Noseda, G. Höbbel, et al. Plasma and fibroblasts of Tangier disease patients are disturbed in transferring phospholipids onto apolipoprotein A-I J. Lipid Res., May 1, 1998; 39(5): 987 - 998. [Abstract] [Full Text]

				B. Garner, P. K. Witting, A. R. Waldeck, J. K. Christison, M. Raftery, and R. Stocker Oxidation of High Density Lipoproteins. I. FORMATION OF METHIONINE SULFOXIDE IN APOLIPOPROTEINS AI AND AII IS AN EARLY EVENT THAT ACCOMPANIES LIPID PEROXIDATION AND CAN BE ENHANCED BY alpha -TOCOPHEROL J. Biol. Chem., March 13, 1998; 273(11): 6080 - 6087. [Abstract] [Full Text] [PDF]

				B. Garner, A. R. Waldeck, P. K. Witting, K.-A. Rye, and R. Stocker Oxidation of High Density Lipoproteins. II. EVIDENCE FOR DIRECT REDUCTION OF LIPID HYDROPEROXIDES BY METHIONINE RESIDUES OF APOLIPOPROTEINS AI AND AII J. Biol. Chem., March 13, 1998; 273(11): 6088 - 6095. [Abstract] [Full Text] [PDF]

				Y. Huang, Y. Zhu, C. Langer, M. Raabe, S. Wu, B. Wiesenhutter, U. Seedorf, N. Maeda, G. Assmann, and A. von Eckardstein Effects of Genotype and Diet on Cholesterol Efflux into Plasma and Lipoproteins of Normal, Apolipoprotein A-I-, and Apolipoprotein E-Deficient Mice Arterioscler. Thromb. Vasc. Biol., October 1, 1997; 17(10): 2010 - 2019. [Abstract] [Full Text]

				R. L. Levine, L. Mosoni, B. S. Berlett, and E. R. Stadtman Methionine residues as endogenous antioxidants in proteins PNAS, December 24, 1996; 93(26): 15036 - 15040. [Abstract] [Full Text] [PDF]

				Y. Huang, A. von Eckardstein, S. Wu, C. Langer, and G. Assmann Generation of Pre-ß1-HDL and Conversion Into {alpha}-HDL : Evidence for Disturbed HDL Conversion in Tangier Disease Arterioscler. Thromb. Vasc. Biol., October 1, 1995; 15(10): 1746 - 1754. [Abstract] [Full Text]

				U. Panzenbock, L. Kritharides, M. Raftery, K.-A. Rye, and R. Stocker Oxidation of Methionine Residues to Methionine Sulfoxides Does Not Decrease Potential Antiatherogenic Properties of Apolipoprotein A-I J. Biol. Chem., June 23, 2000; 275(26): 19536 - 19544. [Abstract] [Full Text] [PDF]