Membrane Protein Production in Lactococcus lactis for Structural Studies

Methods Mol Biol. 2020:2127:29-45. doi: 10.1007/978-1-0716-0373-4_3.

Abstract

The expression and downstream purification of membrane proteins is the prerequisite for biophysical and structural studies of this major source of therapeutic targets. The gram-positive bacterium Lactococcus lactis is an attractive option for heterologous membrane protein expression and purification thanks to advantageous characteristics such as mild proteolytic activity and small genome size. Vectors designed for gene transcription under the control of inducible promoters are readily available. Specifically, the tightly regulated nisin-inducible gene expression system (NICE) allows to fine-tune the overexpression of different gene products. The expressed protein engineered with a suitable tag can be readily detected and purified from crude membrane extracts. The purpose of this protocol chapter is to detail the procedures of cloning, expression, isolation of the membrane vesicles, and affinity purification of a membrane protein of interest in L. lactis.

Keywords: Lactococcus lactis; Membrane protein; NICE expression system; Ni-NTA affinity chromatography; pNZ8148.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Membrane / chemistry
  • Cell Membrane / metabolism
  • Chemical Fractionation / methods
  • Cloning, Molecular / methods*
  • Crystallography, X-Ray / methods
  • Electron Spin Resonance Spectroscopy / methods
  • Gene Expression Regulation, Bacterial
  • Genetic Vectors
  • Lactococcus lactis* / chemistry
  • Lactococcus lactis* / genetics
  • Lactococcus lactis* / metabolism
  • Mass Spectrometry / methods
  • Membrane Proteins* / chemistry
  • Membrane Proteins* / genetics
  • Membrane Proteins* / isolation & purification
  • Membrane Proteins* / metabolism
  • Nisin / chemistry
  • Nisin / genetics
  • Nisin / metabolism
  • Organisms, Genetically Modified
  • Protein Conformation*
  • Recombinant Proteins* / chemistry
  • Recombinant Proteins* / genetics
  • Recombinant Proteins* / isolation & purification
  • Recombinant Proteins* / metabolism
  • Spectrometry, Fluorescence / methods
  • Transformation, Bacterial

Substances

  • Membrane Proteins
  • Recombinant Proteins
  • Nisin
  • nisin A