Expression and purification of mammalian calreticulin in Pichia pastoris

Protein Expr Purif. 2000 Nov;20(2):207-15. doi: 10.1006/prep.2000.1291.

Abstract

Calreticulin is a 46-kDa Ca(2+)-binding chaperone of the endoplasmic reticulum membranes. The protein binds Ca(2+) with high capacity, affects intracellular Ca(2+) homeostasis, and functions as a lectin-like chaperone. In this study, we describe expression and purification procedures for the isolation of recombinant rabbit calreticulin. The calreticulin was expressed in Pichia pastoris and purified to homogeneity by DEAE-Sepharose and Resource Q FPLC chromatography. The protein was not retained in the endoplasmic reticulum of Pichia pastoris but instead it was secreted into the external media. The purification procedures reported here for recombinant calreticulin yield homogeneous preparations of the protein by SDS-PAGE and mass spectroscopy analysis. Purified calreticulin was identified by its NH(2)-terminal amino acid sequences, by its Ca(2+) binding, and by its reactivity with anti-calreticulin antibodies. The protein contained one disulfide bond between (88)Cys and (120)Cys. CD spectral analysis and Ca(2+)-binding properties of the recombinant protein indicated that it was correctly folded.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Calcium Radioisotopes
  • Calcium-Binding Proteins / biosynthesis*
  • Calcium-Binding Proteins / chemistry
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / isolation & purification*
  • Calreticulin
  • Circular Dichroism
  • Disulfides / metabolism
  • Dogs
  • Electrophoresis, Polyacrylamide Gel
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Pichia / genetics*
  • Protein Folding
  • Protein Sorting Signals
  • Rabbits
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Retina / cytology
  • Ribonucleoproteins / biosynthesis*
  • Ribonucleoproteins / chemistry
  • Ribonucleoproteins / genetics
  • Ribonucleoproteins / isolation & purification*
  • Sequence Analysis, Protein
  • Spectrometry, Mass, Electrospray Ionization

Substances

  • Calcium Radioisotopes
  • Calcium-Binding Proteins
  • Calreticulin
  • Disulfides
  • Protein Sorting Signals
  • Recombinant Proteins
  • Ribonucleoproteins