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.

journal_name

J Lipid Res

authors

Dong H,Zhao Z,LeBrun DG,Michaely P

doi

10.1194/jlr.M070938

subject

Has Abstract

pub_date

2017-02-01 00:00:00

pages

364-374

issue

2

eissn

0022-2275

issn

1539-7262

pii

jlr.M070938

journal_volume

58

pub_type

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