Structure of the microsomal triglyceride transfer protein in complex with protein disulfide isomerase

James Thompson, Jack Sack, Harris Jamil, John Wetterau, Howard Einsphr, Leonard Banaszak

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

A crystal structure of microsomal triglycéride transfer protein (MTP, 97 kDa) and protein disulfide isomera.se (PDI, 55 kDa) was obtained by multiple isomorphous replacement and refinement is now underway to 3 A resolution. The MTP-PD1 complex is found in thf lumen of the o.ndoplasmic reticulum. The complex is required for the assembly and secretion of lipoproteins containing apoli, principally very lew density lipoprotoiiis and chylornicrons. Abnormalities in the MTP gene can cause abetalipoproteinemia, a condition where these lipoproteins are riot present in plasma. 'I he MTP model is homologous to the lipovitellin structure, a lipid storage protein found in egg yolk1. However, there are large positional differences between the N terminal and C-terminal domains of MTP and lipovitellin which partly form the lipid binding cavity. These differences redu1 the cavity volume of MTP which may explain its lower lipid binding capacity. The PDI maintains the solubility of MTP. Each of the four domains of PDI has a thioredoxin-like fold and a comparison is made with published NMII structures of the first two domains2'3. The interaction-4 between MTP and PDI will be highlighted. (Supported by a NIH grant, GM13925) 'ShouldersJ. J..Struct. Hiol. U5):2S5-2%. 1994. 2Kemmink et. ai. Biochemistry :r>:7fW'1 7(><H. !996. :lKmmink tt ai. Current Biul. 7(-11:239-15, 19H7.

Original languageEnglish (US)
Pages (from-to)A1381
JournalFASEB Journal
Volume12
Issue number8
StatePublished - Dec 1 1998

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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    Thompson, J., Sack, J., Jamil, H., Wetterau, J., Einsphr, H., & Banaszak, L. (1998). Structure of the microsomal triglyceride transfer protein in complex with protein disulfide isomerase. FASEB Journal, 12(8), A1381.