Abstract
Abstract 026: Apolipoprotein A-I Helical Registry Modulates Lecithin:cholesterol Acyl Transferase Activity
Arteriosclerosis, thrombosis, and vascular biology, Vol.38(Suppl_1)
05/2018
DOI: 10.1161/atvb.38.suppl_1.026
Abstract
Abstract only
The structure of apolipoprotein (APOA1), the major protein of high density lipoproteins (HDL), can modulate protein interactions affecting the cardioprotective functions of HDL particles. APOA1 on nascent discoidal HDL is composed of ten, tandem, α-helical repeats arranged in an anti-parallel, stacked ring-structure that encapsulates a lipid bilayer. Previous chemical cross-linking studies suggested that these APOA1 rings may adopt two different orientations, or registries, with respect to each other. These orientations include one where the bulk of APOA1 orients with the 5
th
helix of one molecule opposing the 5
th
helix of the other (5/5 helical registry), and another orientation adopting a 5/2 helical registry. Engineered HDL particles locked in both 5/5 and 5/2 registries, or rotamers, equally promoted cholesterol efflux from macrophages, indicating functional particles. However, the ability of lecithin:cholesterol acyl transferase (LCAT) to esterify cholesterol was increased over WT in the 5/5 rotamer, and dramatically impaired in the 5/2 rotamer (
p<0.001
), despite surface plasmon resonance studies showing that LCAT bound equally to both. Cross-linking experiments indicated that LCAT activity requires a hybrid epitope composed of helices 5-7 on one APOA1 molecule and 3-4 on the other. Thus, the reciprocating nature of APOA1’s structure may represent a thumbwheel mechanism that influences the activity of HDL remodeling factors in plasma.
Details
- Title: Subtitle
- Abstract 026: Apolipoprotein A-I Helical Registry Modulates Lecithin:cholesterol Acyl Transferase Activity
- Creators
- Allison L Cooke - University of CincinnatiJamie C Morris - University of CincinnatiJohn T Melchior - University of CincinnatiW. G Jerome - Vanderbilt UniversityScott E Street - University of CincinnatiThomas B Thompson - University of CincinnatiLoren E Smith - Vanderbilt UniversityAmy S Shah - Cincinnati Children's Hospital Medical CenterAndrew Herr - Cincinnati Children's Hospital Medical CenterJere P Segrest - Vanderbilt UniversityJay W Heinecke - Seattle UniversityW S Davidson - Davidson College
- Resource Type
- Abstract
- Publication Details
- Arteriosclerosis, thrombosis, and vascular biology, Vol.38(Suppl_1)
- DOI
- 10.1161/atvb.38.suppl_1.026
- ISSN
- 1079-5642
- eISSN
- 1524-4636
- Publisher
- LIPPINCOTT WILLIAMS & WILKINS; PHILADELPHIA
- Language
- English
- Date published
- 05/2018
- Academic Unit
- Anesthesia
- Record Identifier
- 9984958346202771
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