Direct Cloning Method for Expression of Recombinant Proteins with an Inositol Hexakisphosphate Inducible Self-Cleaving Tag

Methods Mol Biol. 2020:2091:163-179. doi: 10.1007/978-1-0716-0167-9_15.

Abstract

Protein purification is the most basic and critical step for protein biophysical and biochemical studies to understand its function and structure. Various fusion tags and proteases have been developed and assembled in expression and purification system. However, it is one of the fields that continues to innovate to develop improved systems that are more efficient, simpler, and less expensive. An efficient self-cleavage C-terminal fusion system was developed using the inositol hexakisphosphate-inducible Vibrio cholerae MARTXVc toxin cysteine protease domain (CPD). CPD fusion proteins are expressed from the T7 promoter and purified using a 6xHis-tag with immobilized-metal affinity chromatography. The C-terminal CPD-tag is removed by self-cleavage at the final purification stage. Here, we describe an efficient cloning method using Gibson assembly, followed by expression and purification of tagless recombinant proteins of interest using CPD self-cleavage.

Keywords: CPD; Cloning; Gibson assembly; IMAC; IP6; Inositol hexakisphosphate; InsP6; Protein expression; Protein purification; SDS-PAGE; Self-cleavage fusion tag.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Bacterial Toxins / chemistry*
  • Bacterial Toxins / genetics
  • Chromatography, Affinity
  • Cloning, Molecular / methods*
  • Histidine / chemistry
  • Phytic Acid / metabolism*
  • Protein Domains
  • Protein Engineering
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Vibrio cholerae / metabolism*

Substances

  • Bacterial Proteins
  • Bacterial Toxins
  • Recombinant Fusion Proteins
  • RtxA protein, Vibrio cholerae
  • Histidine
  • Phytic Acid