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. doi: 10.1038/nsmb.3501. Epub 2017 Nov 13.


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.

MeSH terms

  • Apolipoprotein A-I / metabolism*
  • Cardiotonic Agents / metabolism
  • Computer Simulation
  • Crystallography, X-Ray
  • Humans
  • Lipoproteins, HDL / biosynthesis*
  • Lipoproteins, HDL / metabolism*
  • Models, Molecular*
  • Protein Structure, Secondary


  • Apolipoprotein A-I
  • Cardiotonic Agents
  • Lipoproteins, HDL