A functional polymorphism of apolipoprotein C1 detected by mass spectrometry

Matthew S. Wroblewski, Joshua T. Wilson-Grady, Michael B. Martinez, Raj S. Kasthuri, Kenneth R. McMillan, Cristina Flood-Urdangarin, Gary L Nelsestuen

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

A survey of plasma proteins in approximately 1300 individuals by MALDI-TOF MS resulted in identification of a structural polymorphism of apolipoprotein C1 (ApoC1) that was found only in persons of American Indian or Mexican ancestry. MS/MS analysis revealed that the alteration consisted of a T45S variation. The methyl group of T45 forms part of the lipid-interacting surface of ApoC1. In agreement with an impact on lipid contact, the S45 variant was more susceptible to N-terminal truncation by dipeptidylpeptidase IV in vitro than was the T45 variant. The S45 protein also displayed greater N-terminal truncation (loss of Thr-Pro) in vivo than the T45 variant. The S45 variant also showed preferential distribution to the very-low-density lipoprotein fraction than the T45 protein. These properties indicate a functional effect of the S45 variant and support a role for residue 45 in lipid contact and lipid specificity. Further studies are needed to determine the effects of the variant and its altered N-terminal truncation on the metabolic functions of ApoC1.

Original languageEnglish (US)
Pages (from-to)4707-4715
Number of pages9
JournalFEBS Journal
Volume273
Issue number20
DOIs
StatePublished - Oct 2006

Keywords

  • Apolipoprotein C1
  • Mass spectrometry
  • Polymorphism
  • Protein-lipid contact surface

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    Wroblewski, M. S., Wilson-Grady, J. T., Martinez, M. B., Kasthuri, R. S., McMillan, K. R., Flood-Urdangarin, C., & Nelsestuen, G. L. (2006). A functional polymorphism of apolipoprotein C1 detected by mass spectrometry. FEBS Journal, 273(20), 4707-4715. https://doi.org/10.1111/j.1742-4658.2006.05473.x