TY - JOUR
T1 - Identification of roles for H264, H306, H439, and H635 in acid-dependent lipoprotein release by the LDL receptor
AU - Dong, Hongyun
AU - Zhao, Zhenze
AU - LeBrun, Drake G.
AU - Michaely, Peter
N1 - Publisher Copyright:
Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.
PY - 2017
Y1 - 2017
N2 - Lipoproteins internalized by the LDL receptor (LDLR) are released from this receptor in endosomes through a process that involves acid-dependent conformational changes in the receptor ectodomain. How acidic pH promotes this release process is not well understood. Here, we assessed roles for six histidine residues for which either genetic or structural data suggested a possible role in the acid-responsiveness of the LDLR. Using assays that measured conformational change, acid-dependent lipoprotein release, LDLR recycling, and net lipoprotein uptake, we show that H635 plays important roles in acid-dependent conformational change and lipoprotein release, while H264, H306, and H439 play ancillary roles in the response of the LDLR to acidic pH.-Dong, H., Z. Zhao, D. G. LeBrun, and P. Michaely. Identification of roles for H264, H306, H439, and H635 in acid-dependent lipoprotein release by the LDL receptor.
AB - Lipoproteins internalized by the LDL receptor (LDLR) are released from this receptor in endosomes through a process that involves acid-dependent conformational changes in the receptor ectodomain. How acidic pH promotes this release process is not well understood. Here, we assessed roles for six histidine residues for which either genetic or structural data suggested a possible role in the acid-responsiveness of the LDLR. Using assays that measured conformational change, acid-dependent lipoprotein release, LDLR recycling, and net lipoprotein uptake, we show that H635 plays important roles in acid-dependent conformational change and lipoprotein release, while H264, H306, and H439 play ancillary roles in the response of the LDLR to acidic pH.-Dong, H., Z. Zhao, D. G. LeBrun, and P. Michaely. Identification of roles for H264, H306, H439, and H635 in acid-dependent lipoprotein release by the LDL receptor.
KW - Dyslipidemias
KW - Endocytosis
KW - Lipoproteins/metabolism
KW - Lipoproteins/receptors
KW - Low density lipoprotein
UR - http://www.scopus.com/inward/record.url?scp=85011277377&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85011277377&partnerID=8YFLogxK
U2 - 10.1194/jlr.M070938
DO - 10.1194/jlr.M070938
M3 - Article
C2 - 27895090
AN - SCOPUS:85011277377
SN - 0022-2275
VL - 58
SP - 364
EP - 374
JO - Journal of lipid research
JF - Journal of lipid research
IS - 2
ER -