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Jens Lagerstedt

Associate professor

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Structures of apolipoprotein A-I in high density lipoprotein generated by electron microscopy and biased simulations


  • Lin Zhu
  • Jitka Petrlova
  • Peter Gysbers
  • Hans Hebert
  • Stefan Wallin
  • Caroline Jegerschöld
  • Jens Lagerstedt

Summary, in English

Background: Apolipoprotein A-I (apoA-I) in high-density lipoprotein (HDL) is a key protein for the transport of cholesterol from the vascular wall to the liver. The formation and structure of nascent HDL, composed of apoA-I and phospholipids, is critical to this process. Methods: The HDL was assembled in vitro from apoA-I, cholesterol and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) at a 1:4:50 molar ratio. The structure of HDL was investigated in vitreous samples, frozen at cryogenic temperatures, as well as in negatively stained samples by transmission electron microscopy. Low resolution electron density maps were next used as restraints in biased Monte Carlo simulations of apolipoprotein A-I dimers, with an initial structure derived from atomic resolution X-ray structures. Results: Two final apoA-I structure models for the full-length structure of apoA-I dimer in the lipid bound conformation were generated, showing a nearly circular, flat particle with an uneven particle thickness. Conclusions: The generated structures provide evidence for the discoidal, antiparallel arrangement of apoA-I in nascent HDL, and propose two preferred conformations of the flexible N-termini. General significance: The novel full-length structures of apoA-I dimers deepens the understanding to the structure-function relationship of nascent HDL with significance for the prevention of lipoprotein-related disease. The biased simulation method used in this study provides a powerful and convenient modelling tool with applicability for structural studies and modelling of other proteins and protein complexes.


  • Schmidtchen Lab
  • Medical Protein Science
  • EXODIAB: Excellence of Diabetes Research in Sweden

Publishing year







Biochimica et Biophysica Acta - General Subjects




11, Part A

Document type

Journal article




  • Biophysics


  • Apolipoprotein A-I
  • Biased simulations
  • Cryo-EM
  • HDL
  • Negative stain electron microscopy



Research group

  • Schmidtchen Lab
  • Medical Protein Science


  • ISSN: 0304-4165