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Structural analysis of lecithin:cholesterol acyltransferase bound to high density lipoprotein particles.
Manthei, Kelly A; Patra, Dhabaleswar; Wilson, Christopher J; Fawaz, Maria V; Piersimoni, Lolita; Shenkar, Jenny Capua; Yuan, Wenmin; Andrews, Philip C; Engen, John R; Schwendeman, Anna; Ohi, Melanie D; Tesmer, John J G.
Affiliation
  • Manthei KA; Life Sciences Institute, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Patra D; Departments of Biological Sciences and of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, 47907, USA.
  • Wilson CJ; Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, 02115, USA.
  • Fawaz MV; Department of Medicinal Chemistry, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Piersimoni L; Departments of Biological Chemistry, Bioinformatics and Chemistry, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Shenkar JC; Department of Pharmaceutical Science, Biointerfaces Institute, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Yuan W; Department of Pharmaceutical Science, Biointerfaces Institute, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Andrews PC; Departments of Biological Chemistry, Bioinformatics and Chemistry, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Engen JR; Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, 02115, USA.
  • Schwendeman A; Department of Pharmaceutical Science, Biointerfaces Institute, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Ohi MD; Life Sciences Institute and Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Tesmer JJG; Departments of Biological Sciences and of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, 47907, USA. jtesmer@purdue.edu.
Commun Biol ; 3(1): 28, 2020 01 15.
Article in En | MEDLINE | ID: mdl-31942029
ABSTRACT
Lecithincholesterol acyltransferase (LCAT) catalyzes a critical step of reverse cholesterol transport by esterifying cholesterol in high density lipoprotein (HDL) particles. LCAT is activated by apolipoprotein A-I (ApoA-I), which forms a double belt around HDL, however the manner in which LCAT engages its lipidic substrates and ApoA-I in HDL is poorly understood. Here, we used negative stain electron microscopy, crosslinking, and hydrogen-deuterium exchange studies to refine the molecular details of the LCAT-HDL complex. Our data are consistent with LCAT preferentially binding to the edge of discoidal HDL near the boundary between helix 5 and 6 of ApoA-I in a manner that creates a path from the lipid bilayer to the active site of LCAT. Our results provide not only an explanation why LCAT activity diminishes as HDL particles mature, but also direct support for the anti-parallel double belt model of HDL, with LCAT binding preferentially to the helix 4/6 region.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Protein Conformation / Models, Molecular / Multiprotein Complexes / Phosphatidylcholine-Sterol O-Acyltransferase / Lipoproteins, HDL Language: En Journal: Commun Biol Year: 2020 Document type: Article
Fulltext
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PubMed Links
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Protein Conformation / Models, Molecular / Multiprotein Complexes / Phosphatidylcholine-Sterol O-Acyltransferase / Lipoproteins, HDL Language: En Journal: Commun Biol Year: 2020 Document type: Article