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Structural Studies of High Density Lipoprotein by Electron Microscopy and Flexible Fitting
KTH, School of Technology and Health (STH), Basic Science and Biomedicine, Structural Biotechnology. (Hans Hebert)
(English)Manuscript (preprint) (Other academic)
National Category
Structural Biology
Research subject
Technology and Health
Identifiers
URN: urn:nbn:se:kth:diva-204556OAI: oai:DiVA.org:kth-204556DiVA: diva2:1085154
Note

QC 20170328

Available from: 2017-03-28 Created: 2017-03-28 Last updated: 2017-03-30Bibliographically approved
In thesis
1. Structural studies of HDL and applications of EM on membrane proteins
Open this publication in new window or tab >>Structural studies of HDL and applications of EM on membrane proteins
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

A large number of proteins interact with biological membranes, either integrated in the membrane (PepTSo2), embedded on a membrane surface (5-lipoxygenase) or encircling a cutout of lipid bilayer (apolipoprotein1 (apoA-I). They function as transporters, receptors or biocatalysts in cellular processes like inflammation or cholesterol transport which are touched upon here. Malfunction of specific membrane proteins are the cause for several diseases or disorders.

Knowledge of protein structure supports understanding of its mechanism of function. Here, transmission electron microscopy (TEM) was used for structure determination. To obtain structure information to high resolution for membrane proteins, normally surrounded by lipids, demands specific methods and materials for stabilization. Stabilized in detergent the structure of the bacterial transporter PepTSo2 was shown to form a tetramer even bound to substrate. However, with a protein based stabilizer, Salipro, the structure of PepTSo2 could be determined to high resolution.

High density lipoprotein (HDL) in blood plasma, involved in the removal of cholesterol from peripheral tissues, have a central role in cardiovascular function, metabolic syndrome and diabetes.

The HDL-particle is composed of two copies of ApoA1 and around hundred lipid molecules. From TEM data, for the first time the clearly discoidal shape could be shown by 3-dimendional reconstructions. These were used for modelling the ApoA1 protein dimer by a "biased fitting" procedure. The results indicate how ApoA1 folds around a lipid bilayer in a disc-shaped structure.

Modified HDL called nanodiscs were here used to show the Ca2+ dependent binding of 5-lipoxygenase on the nanodisc bilayer and thereby increased production of the inflammatory mediator leukotrieneA4. Dimerization of 5-lipoxygenase inactivates these functions.

Place, publisher, year, edition, pages
KTH Royal Institute of Technology, 2017. 73 p.
Series
TRITA-STH : report, ISSN 1653-3836 ; 2017:4
Keyword
high density lipoprotein, rHDL, apoA-I, transmission electron microscopy, membrane protein, nanodisc, Salipro, transporter
National Category
Biological Sciences
Research subject
Technology and Health
Identifiers
urn:nbn:se:kth:diva-204045 (URN)978-91-7729-339-2 (ISBN)
Public defence
2017-04-24, T2, Hälsovägen 11C, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

QC 20170323

Available from: 2017-03-23 Created: 2017-03-23 Last updated: 2017-03-28Bibliographically approved

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CiteExportLink to record
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Citation style
  • apa
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