Model of human low-density lipoprotein and bound receptor based on CryoEM

Gang Ren, Gabrielle Rudenko, Steven J. Ludtke, Johann Deisenhofer, Wah Chiu, Henry J. Pownall

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Human plasma low-density lipoproteins (LDL), a risk factor for cardiovascular disease, transfer cholesterol from plasma to liver cells via the LDL receptor (LDLr). Here, we report the structures of LDL and its complex with the LDL receptor extracellular domain (LDL • LDLr) at extracellular pH determined by cryoEM. Difference imaging between LDL • LDLr and LDL localizes the site of LDLr bound to its ligand. The structural features revealed from the cryoEM map lead to a juxtaposed stacking model of cholesteryl esters (CEs). High density in the outer shell identifies protein-rich regions that can be accounted for by a single apolipoprotein (apo B-100, 500 kDa) leading to a model for the distribution of its α-helix and β-sheet rich domains across the surface. The structural relationship between the apo B-100 and CEs appears to dictate the structural stability and function of normal LDL.

Original languageEnglish (US)
Pages (from-to)1059-1064
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number3
DOIs
StatePublished - Jan 19 2010
Externally publishedYes

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LDL Receptors
Apolipoprotein B-100
LDL Lipoproteins
Cholesterol Esters
human LDLR protein
Cardiovascular Diseases
Cholesterol
Ligands
Liver
Proteins

Keywords

  • Apolipoprotein B-100
  • Cholesteryl ester
  • Electron cryomicroscopy
  • LDL receptor

ASJC Scopus subject areas

  • General

Cite this

Model of human low-density lipoprotein and bound receptor based on CryoEM. / Ren, Gang; Rudenko, Gabrielle; Ludtke, Steven J.; Deisenhofer, Johann; Chiu, Wah; Pownall, Henry J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 3, 19.01.2010, p. 1059-1064.

Research output: Contribution to journalArticle

Ren, Gang ; Rudenko, Gabrielle ; Ludtke, Steven J. ; Deisenhofer, Johann ; Chiu, Wah ; Pownall, Henry J. / Model of human low-density lipoprotein and bound receptor based on CryoEM. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 3. pp. 1059-1064.
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