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 language | English (US) |
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Pages (from-to) | 4707-4715 |
Number of pages | 9 |
Journal | FEBS Journal |
Volume | 273 |
Issue number | 20 |
DOIs | |
State | Published - Oct 2006 |
Keywords
- Apolipoprotein C1
- Mass spectrometry
- Polymorphism
- Protein-lipid contact surface