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

Academic Article

Abstract

  • 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 lipidfree 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.
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Melchior JT; Walker RG; Cooke AL; Morris J; Castleberry M; Thompson TB; Jones MK; Song HD; Rye KA; Oda MN
  • Start Page

  • 1093
  • End Page

  • 1099
  • Volume

  • 24
  • Issue

  • 12