A common binding site on the microsomal triglyceride transfer protein for apolipoprotein B and protein disulfide isomerase

Paul Bradbury, Christopher J. Mann, Silvano Köchl, Timothy A. Anderson, S. Ann Chester, John M. Hancock, Penelope J. Ritchie, Joanna Amey, Georgina B. Harrison, David G Levitt, Leonard J. Banaszak, James Scottt, Carol C. Shoulders

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

The assembly of triglyceride-rich lipoproteins requires the formation in the endoplasmic reticulum of a complex between apolipoprotein B (apoB), a microsomal triglyceride transfer protein (MTP), and protein disulfide isomerase (PDI). In the MTP complex, the amino-terminal region of MTP (residues 22-303) interacts with the amino-terminal region of apoB (residues 1-264). Here, we report the identification and characterization of a site on apoB between residues 512 and 721, which interacts with residues 517-603 of MTP. PDI binds in close proximity to this apoB binding site on MTP. The proximity of these binding sites on MTP for PDI and amino acids 512-721 of apoB was evident from studies carried out in a yeast two-hybrid system and by coimmunoprecipitation. The expression of PDI with MTP and apoB16 (residues 1- 721) in the baculovirus expression system reduced the amount of MTP co- immunoprecipitated with apoB by 73%. The interaction of residues 512-721 of apoB with MTP facilitates lipoprotein production. Mutations of apoB that markedly reduced this interaction also reduced the level of apoB-containing lipoprotein secretion.

Original languageEnglish (US)
Pages (from-to)3159-3164
Number of pages6
JournalJournal of Biological Chemistry
Volume274
Issue number5
DOIs
StatePublished - Jan 29 1999

Bibliographical note

Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.

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