TY - JOUR
T1 - Structure of the LDL receptor extracellular domain at endosomal pH
AU - Rudenko, Gabby
AU - Henry, Lisa
AU - Henderson, Keith
AU - Ichtchenko, Konstantin
AU - Brown, Michael S.
AU - Goldstein, Joseph L.
AU - Deisenhofer, Johann
PY - 2002/12/20
Y1 - 2002/12/20
N2 - The low-density lipoprotein receptor mediates cholesterol homeostasis through endocytosis of lipoproteins. It discharges its ligand in the endosome at pH < 6. In the crystal structure at pH = 5.3, the ligand-binding domain (modules R2 to R7) folds back as an arc over the epidermal growth factor precursor homology domain (the modules A, B, β propeller, and C). The modules R4 and R5, which are critical for lipoprotein binding, associate with the β propeller via their calcium-binding loop. We propose a mechanism for lipoprotein release in the endosome whereby the β propeller functions as an alternate substrate for the ligand-binding domain, binding in a calcium-dependent way and promoting lipoprotein release.
AB - The low-density lipoprotein receptor mediates cholesterol homeostasis through endocytosis of lipoproteins. It discharges its ligand in the endosome at pH < 6. In the crystal structure at pH = 5.3, the ligand-binding domain (modules R2 to R7) folds back as an arc over the epidermal growth factor precursor homology domain (the modules A, B, β propeller, and C). The modules R4 and R5, which are critical for lipoprotein binding, associate with the β propeller via their calcium-binding loop. We propose a mechanism for lipoprotein release in the endosome whereby the β propeller functions as an alternate substrate for the ligand-binding domain, binding in a calcium-dependent way and promoting lipoprotein release.
UR - http://www.scopus.com/inward/record.url?scp=0037147281&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037147281&partnerID=8YFLogxK
U2 - 10.1126/science.1078124
DO - 10.1126/science.1078124
M3 - Article
C2 - 12459547
AN - SCOPUS:0037147281
SN - 0036-8075
VL - 298
SP - 2353
EP - 2358
JO - Science
JF - Science
IS - 5602
ER -