Structural analysis of lecithin:cholesterol acyltransferase bound to high density lipoprotein particles

Research output: Contribution to journalArticle

Authors

  • Kelly A. Manthei
  • Dhabaleswar Patra
  • Christopher J. Wilson
  • Maria V. Fawaz
  • Lolita Piersimoni
  • Jenny Capua Shenkar
  • Wenmin Yuan
  • Philip C. Andrews
  • John R. Engen
  • Anna Schwendeman
  • Melanie D. Ohi
  • John J.G. Tesmer

External Institution(s)

  • University of Michigan, Ann Arbor
  • Purdue University
  • Northeastern University

Details

Original languageEnglish (US)
Article number28
JournalCommunications Biology
Volume3
Issue number1
StatusPublished - Dec 1 2020
Peer-reviewedYes

Abstract

Lecithin:cholesterol 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.

Citation formats

APA

Manthei, K. A., Patra, D., Wilson, C. J., Fawaz, M. V., Piersimoni, L., Shenkar, J. C., ... Tesmer, J. J. G. (2020). Structural analysis of lecithin:cholesterol acyltransferase bound to high density lipoprotein particles. Communications Biology, 3(1), [28]. https://doi.org/10.1038/s42003-019-0749-z

Harvard

Manthei, KA, Patra, D, Wilson, CJ, Fawaz, MV, Piersimoni, L, Shenkar, JC, Yuan, W, Andrews, PC, Engen, JR, Schwendeman, A, Ohi, MD & Tesmer, JJG 2020, 'Structural analysis of lecithin:cholesterol acyltransferase bound to high density lipoprotein particles', Communications Biology, vol. 3, no. 1, 28. https://doi.org/10.1038/s42003-019-0749-z