Model of human low-density lipoprotein and bound receptor based on cryoEM.
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 alpha-helix and beta-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.
Ren
Gang
G
Department of Biochemistry & Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA. gren@msg.ucsf.edu
Rudenko
Gabby
G
Ludtke
Steven J
SJ
Deisenhofer
Johann
J
Chiu
Wah
W
Pownall
Henry J
HJ
D020285:Cryoelectron Microscopy / Q000379:methods*; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D011973:Receptors, LDL / Q000737:chemistry*
D011973:Receptors, LDL