A functional polymorphism of apolipoprotein C1 detected by mass spectrometry.
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.
Wroblewski
Matthew S
MS
Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, 55455, USA.
Wilson-Grady
Joshua T
JT
Martinez
Michael B
MB
Kasthuri
Raj S
RS
McMillan
Kenneth R
KR
Flood-Urdangarin
Cristina
C
Nelsestuen
Gary L
GL
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
D053302:Apolipoprotein C-I; D008079:Lipoproteins, VLDL