title: Identification of roles for H264, H306, H439, and H635 in acid-dependent lipoprotein release by the LDL receptor.
abstract: 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.
authors.affiliation: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Hongyun
authors.initials: H
authors.lastname: Dong
authors.affiliation: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Zhenze
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Drake G
authors.initials: DG
authors.lastname: LeBrun
authors.affiliation: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX peter.michaely@utsouthwestern.edu.
authors.forename: Peter
authors.initials: P
authors.lastname: Michaely
mesh_terms: D000818:Animals; D002460:Cell Line; D004705:Endocytosis / Q000235:genetics; D011992:Endosomes / Q000737:chemistry / Q000378:metabolism; D006639:Histidine / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008074:Lipoproteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D011973:Receptors, LDL / Q000737:chemistry* / Q000378:metabolism
chemical_list: C573412:LDLR protein, human; D008074:Lipoproteins; D011973:Receptors, LDL; D006639:Histidine
keywords: dyslipidemias; endocytosis; lipoproteins/metabolism; lipoproteins/receptors; low density lipoprotein