HSP90, HSP70, and GAPDH directly interact with the cytoplasmic domain of macrophage scavenger receptors

Biochem Biophys Res Commun. 2002 Jan 18;290(2):858-64. doi: 10.1006/bbrc.2001.6271.

Abstract

The macrophage scavenger receptor (MSR) is a trimeric membrane protein which binds to modified low-density lipoprotein (LDL) and has been indicated in the development of atherosclerosis. It has recently been demonstrated that the N-terminal cytoplasmic domain of MSR has an important role in the efficient internalization and cell-surface expression of the receptor. This study shows that the N-terminal cytoplasmic domain in bovine was constructed using a peptide architecture technique in which the peptide chain was bundled at their C-terminus to yield a trimeric form and that this did not form an ordered structure. Furthermore, the binding proteins to the cytoplasmic domain of MSR were determined for the first time using a peptide affinity column. Sequence analyses of the specific binding proteins in bovine revealed that heat shock protein 90 (HSP90), heat shock protein 70 (HSP70), leucine aminopeptidase (LAP), adenocylhomocysteinase, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) were included. GST-pull-down assay and immunoprecipitation analyses on HSP90, HSP70, and GAPDH showed that all these proteins could bind to the cytoplasmic domain of MSR in vitro and in vivo. These proteins interact with the cytoplasmic domain directly and may have an effect on the functions of MSR such as internalization, cell-surface expression, and signal transduction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • COS Cells
  • Cattle
  • Chromatography, Affinity
  • Circular Dichroism
  • Electrophoresis, Polyacrylamide Gel
  • Glyceraldehyde-3-Phosphate Dehydrogenases / genetics
  • Glyceraldehyde-3-Phosphate Dehydrogenases / metabolism*
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism*
  • HSP90 Heat-Shock Proteins / genetics
  • HSP90 Heat-Shock Proteins / metabolism*
  • Humans
  • Lung / chemistry
  • Lung / metabolism
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Precipitin Tests
  • Protein Binding / physiology
  • Protein Structure, Tertiary / physiology
  • Receptors, Immunologic / chemistry*
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Receptors, Scavenger
  • Scavenger Receptors, Class A
  • Structure-Activity Relationship

Substances

  • HSP70 Heat-Shock Proteins
  • HSP90 Heat-Shock Proteins
  • MSR1 protein, human
  • Peptide Fragments
  • Receptors, Immunologic
  • Receptors, Scavenger
  • Scavenger Receptors, Class A
  • Glyceraldehyde-3-Phosphate Dehydrogenases