Nature Structural and Molecular Biology
Nature Structural and Molecular Biology
5 years ago

A consensus model of human apolipoprotein A-I in its monomeric and lipid-free state

A consensus model of human apolipoprotein A-I in its monomeric and lipid-free state
Jay W Heinecke, Mark Castleberry, Sissel Lund-Katz, Martin K Jones, John T Melchior, Xiaohu Mei, Ryan G Walker, Mary G Sorci-Thomas, Thomas B Thompson, Jere P Segrest, David Atkinson, Jamie Morris, Allison L Cooke, Michael J Thomas, Michael C Phillips, Michael N Oda, Hyun D Song, W Sean Davidson, Kerry-Anne Rye
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.

Publisher URL: https://www.nature.com/articles/nsmb.3501

DOI: 10.1038/nsmb.3501

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