TAILIEUCHUNG - Báo cáo khoa học: A functional polymorphism of apolipoprotein C1 detected by mass spectrometry

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. | ỊFEBS Journal A functional polymorphism of apolipoprotein C1 detected by mass spectrometry Matthew S. Wroblewski1 Joshua T. Wilson-Grady1 Michael B. Martinez1 Raj S. Kasthuri2 Kenneth R. McMillan3 Cristina Flood-Urdangarin4 and Gary L. Nelsestuen1 1 Department of Biochemistry Molecular Biology and Biophysics University of Minnesota Minneapolis MN USA 2 Department of Medicine University of Minnesota Minneapolis MN USA 3 American Indian Community Development Corporation Minneapolis MN USA 4 St Mary s Health Clinics St Paul MN USA Keywords apolipoprotein C1 mass spectrometry polymorphism protein lipid contact surface Correspondence G. L. Nelsestuen 6-155 Jackson Hall 321 Church St SE Minneapolis MN 55455 USA Fax 612 625 2163 Tel 612 624 3622 E-mail nelse002@ Received 7 July 2006 revised 16 August 2006 accepted 18 August 2006 doi 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. Apolipoprotein C1 ApoC1 is a component of very-low-density

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