A consensus model of human apolipoprotein A-I in its monomeric and lipid-free state. Nat Struct Mol Biol 2017 Dec;24(12):1093-1099
Date
11/14/2017Pubmed ID
29131142Pubmed Central ID
PMC5749415DOI
10.1038/nsmb.3501Scopus ID
2-s2.0-85039561595 (requires institutional sign-in at Scopus site) 46 CitationsAbstract
Apolipoprotein (apo)A-I is an organizing scaffold protein that is critical to high-density lipoprotein (HDL) structure and metabolism, probably mediating many of its cardioprotective properties. However, HDL biogenesis is poorly understood, as lipid-free apoA-I has been notoriously resistant to high-resolution structural study. Published models from low-resolution techniques share certain features but vary considerably in shape and secondary structure. To tackle this central issue in lipoprotein biology, we assembled a team of structural biologists specializing in apolipoproteins and set out to build a consensus model of monomeric lipid-free human apoA-I. Combining novel and published cross-link constraints, small-angle X-ray scattering (SAXS), hydrogen-deuterium exchange (HDX) and crystallography data, we propose a time-averaged model consistent with much of the experimental data published over the last 40 years. The model provides a long-sought platform for understanding and testing details of HDL biogenesis, structure and function.
Author List
Melchior JT, Walker RG, Cooke AL, Morris J, Castleberry M, Thompson TB, Jones MK, Song HD, Rye KA, Oda MN, Sorci-Thomas MG, Thomas MJ, Heinecke JW, Mei X, Atkinson D, Segrest JP, Lund-Katz S, Phillips MC, Davidson WSAuthors
Mary Sorci Thomas PhD Professor in the Medicine department at Medical College of WisconsinMichael J. Thomas PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Apolipoprotein A-ICardiotonic Agents
Computer Simulation
Crystallography, X-Ray
Humans
Lipoproteins, HDL
Models, Molecular
Protein Structure, Secondary
