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Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Cisse, A; Desfosses, A; Stainer, S; Kandiah, E; Traore, DAK; Bezault, A; Schachner-Nedherer, AL; Leitinger, G; Hoerl, G; Hinterdorfer, P; Gutsche, I; Prassl, R; Peters, J; Kornmueller, K.
Targeting structural flexibility in low density lipoprotein by integrating cryo-electron microscopy and high-speed atomic force microscopy.
Int J Biol Macromol. 2023; 252: 126345
Doi: 10.1016/j.ijbiomac.2023.126345
Web of Science
PubMed
FullText
FullText_MUG
- Leading authors Med Uni Graz
- Kornmüller Karin
- Co-authors Med Uni Graz
- Hörl Gerd
- Leitinger Gerd
- Prassl Ruth
- Schachner-Nedherer Anna-Laurence
- Stainer Sarah
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- Abstract:
- Low-density lipoprotein (LDL) plays a crucial role in cholesterol metabolism. Responsible for cholesterol transport from the liver to the organs, LDL accumulation in the arteries is a primary cause of cardiovascular diseases, such as atherosclerosis. This work focuses on the fundamental question of the LDL molecular structure, as well as the topology and molecular motions of apolipoprotein B-100 (apo B-100), which is addressed by single-particle cryo-electron microscopy (cryo-EM) and high-speed atomic force microscopy (HS-AFM). Our results suggest a revised model of the LDL core organization with respect to the cholesterol ester (CE) arrangement. In addition, a high-density region close to the flattened poles could be identified, likely enriched in free cholesterol. The most remarkable new details are two protrusions on the LDL surface, attributed to the protein apo B-100. HS-AFM adds the dimension of time and reveals for the first time a highly dynamic direct description of LDL, where we could follow large domain fluctuations of the protrusions in real time. To tackle the inherent flexibility and heterogeneity of LDL, the cryo-EM maps are further assessed by 3D variability analysis. Our study gives a detailed explanation how to approach the intrinsic flexibility of a complex system comprising lipids and protein.
- Find related publications in this database (using NLM MeSH Indexing)
- Lipoproteins, LDL - metabolism
- Cryoelectron Microscopy - administration & dosage
- Apolipoprotein B-100 - administration & dosage
- Microscopy, Atomic Force - methods
- Cholesterol - administration & dosage
- Find related publications in this database (Keywords)
- Low density lipoprotein
- LDL
- Apolipoprotein B-100
- Apo B-100
- Cryo-electron microscopy
- High speed atomic force microscopy
- Flexibility