Expression and Purification of a Functional E. coli 13CH3-Methionine-Labeled Thermostable Neurotensin Receptor 1 Variant for Solution NMR Studies

Fabian Bumbak, Ross A.D. Bathgate, Daniel J. Scott, Paul R. Gooley

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Otherpeer-review

4 Citations (Scopus)

Abstract

Escherichia coli (E. coli) is the most widely used expression host for recombinant proteins due to high expression yields and straightforward molecular cloning. Directed evolution of G protein-coupled receptors (GPCRs) has made several of these difficult to express membrane proteins amenable to prokaryotic expression. Here, we describe a protocol for near complete 13CH3-methionine labeling of a thermostable neurotensin receptor 1 (enNTS1) variant in E. coli for solution NMR-based dynamics studies. Our expression strategy utilizes methionine biosynthesis pathway inhibition forcing E. coli to incorporate exogenous methionine with 96% efficiency at expression levels of 2.6 mg enNTS1 per liter of expression culture containing 50 mg of 13CH3-methionine. We also provide a 3-step purification protocol that produces final yields of 0.6 mg of functional Apo-state enNTS1.

Original languageEnglish
Title of host publicationMethods in Molecular Biology
PublisherHumana Press
Pages31-55
Number of pages25
DOIs
Publication statusPublished - 2019
Externally publishedYes

Publication series

NameMethods in Molecular Biology
Volume1947
ISSN (Print)1064-3745
ISSN (Electronic)1940-6029

Keywords

  • CH-methionine
  • Apo-state
  • E. coli
  • GPCR
  • Membrane protein
  • Neurotensin receptor 1
  • Thermostable

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