title: A functional polymorphism of apolipoprotein C1 detected by mass spectrometry.
abstract: A survey of plasma proteins in approximately 1,300 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.
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, 55455, USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Wroblewski
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Wilson-Grady
authors.forename: Michael B
authors.initials: MB
authors.lastname: Martinez
authors.forename: Raj S
authors.initials: RS
authors.lastname: Kasthuri
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: McMillan
authors.forename: Cristina
authors.initials: C
authors.lastname: Flood-Urdangarin
authors.forename: Gary L
authors.initials: GL
authors.lastname: Nelsestuen
mesh_terms: D001741:Black or African American / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D053302:Apolipoprotein C-I / Q000097:blood / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D008079:Lipoproteins, VLDL / Q000097:blood; D017058:Mexican Americans / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D016415:Sequence Alignment; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D053302:Apolipoprotein C-I; D008079:Lipoproteins, VLDL