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
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U2 - 10.1073/pnas.0908004107
DO - 10.1073/pnas.0908004107
M3 - Article
C2 - 20080547
AN - SCOPUS:75749112129
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
SN - 0027-8424
IS - 3
ER -