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

Gang Ren; Gabby Rudenko; Steven J. Ludtke; Johann Deisenhofer; Wah Chiu; Henry J. Pownall

doi:10.1073/pnas.0908004107

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

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

Research output: Contribution to journal › Article › peer-review

68 Scopus citations

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 language	English (US)
Pages (from-to)	1059-1064
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	107
Issue number	3
DOIs	https://doi.org/10.1073/pnas.0908004107
State	Published - Jan 19 2010

Keywords

Apolipoprotein B-100
Cholesteryl ester
Electron cryomicroscopy
LDL receptor

ASJC Scopus subject areas

General

Access to Document

10.1073/pnas.0908004107

Cite this

@article{9e524c5757a2417ca61977cca29346ca,

title = "Model of human low-density lipoprotein and bound receptor based on CryoEM",

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.",

keywords = "Apolipoprotein B-100, Cholesteryl ester, Electron cryomicroscopy, LDL receptor",

author = "Gang Ren and Gabby Rudenko and Ludtke, {Steven J.} and Johann Deisenhofer and Wah Chiu and Pownall, {Henry J.}",

year = "2010",

month = jan,

day = "19",

doi = "10.1073/pnas.0908004107",

language = "English (US)",

volume = "107",

pages = "1059--1064",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences",

number = "3",

}

TY - JOUR

T1 - Model of human low-density lipoprotein and bound receptor based on CryoEM

AU - Ren, Gang

AU - Rudenko, Gabby

AU - Ludtke, Steven J.

AU - Deisenhofer, Johann

AU - Chiu, Wah

AU - Pownall, Henry J.

PY - 2010/1/19

Y1 - 2010/1/19

N2 - 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.

AB - 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.

KW - Apolipoprotein B-100

KW - Cholesteryl ester

KW - Electron cryomicroscopy

KW - LDL receptor

UR - http://www.scopus.com/inward/record.url?scp=75749112129&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=75749112129&partnerID=8YFLogxK

U2 - 10.1073/pnas.0908004107

DO - 10.1073/pnas.0908004107

M3 - Article

C2 - 20080547

AN - SCOPUS:75749112129

SN - 0027-8424

VL - 107

SP - 1059

EP - 1064

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 3

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this