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Structures of apolipoprotein A-I in high density lipoprotein generated by electron microscopy and biased simulations
KTH, School of Technology and Health (STH), Medical Engineering, Structural Biotechnology. Karolinska Institutet, Sweden.
KTH, School of Technology and Health (STH), Medical Engineering, Structural Biotechnology. Karolinska Institutet, Sweden.ORCID iD: 0000-0002-3220-9402
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2017 (English)In: Biochimica et Biophysica Acta - General Subjects, ISSN 0304-4165, E-ISSN 1872-8006, Vol. 1861, no 11, 2726-2738 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Elsevier, 2017. Vol. 1861, no 11, 2726-2738 p.
Keyword [en]
Apolipoprotein A-I, Biased simulations, Cryo-EM, HDL, Negative stain electron microscopy, 2 oleoyl 1 palmitoylphosphatidylcholine, apolipoprotein A1, cholesterol, dimer, high density lipoprotein, amino terminal sequence, Article, disorders of lipoprotein metabolism, electron, electron microscopy, image analysis, in vitro study, priority journal, protein analysis, protein lipid interaction, protein modification, protein structure, simulation, temperature, transmission electron microscopy
National Category
Structural Biology
Identifiers
URN: urn:nbn:se:kth:diva-218631DOI: 10.1016/j.bbagen.2017.07.017ISI: 000415768500022PubMedID: 28754383Scopus ID: 2-s2.0-85026642644OAI: oai:DiVA.org:kth-218631DiVA: diva2:1161446
Funder
Swedish Research Council, K2014-54X-22426-01-3The Wenner-Gren Foundation
Note

QC 20171130

Available from: 2017-11-30 Created: 2017-11-30 Last updated: 2017-12-07Bibliographically approved

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Zhu, LinHebert, Hans

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