Identification of roles for H264, H306, H439, and H635 in acid-dependent lipoprotein release by the LDL receptor

Hongyun Dong, Zhenze Zhao, Drake G. LeBrun, Peter Michaely

Research output: Contribution to journalArticle

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.-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.

Original languageEnglish (US)
Pages (from-to)364-374
Number of pages11
JournalJournal of Lipid Research
Volume58
Issue number2
DOIs
StatePublished - 2017

Fingerprint

LDL Receptors
Lipoproteins
Acids
Endosomes
Recycling
Histidine
Assays

Keywords

  • Dyslipidemias
  • Endocytosis
  • Lipoproteins/metabolism
  • Lipoproteins/receptors
  • Low density lipoprotein

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Identification of roles for H264, H306, H439, and H635 in acid-dependent lipoprotein release by the LDL receptor. / Dong, Hongyun; Zhao, Zhenze; LeBrun, Drake G.; Michaely, Peter.

In: Journal of Lipid Research, Vol. 58, No. 2, 2017, p. 364-374.

Research output: Contribution to journalArticle

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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.-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.",
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AU - Michaely, Peter

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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.

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