Fine Sampling of Sequence Space for Membrane Protein Structural Biology

J Mol Biol. 2021 Jul 23;433(15):167055. doi: 10.1016/j.jmb.2021.167055. Epub 2021 May 20.

Abstract

We describe an enhancement of traditional genomics-based approaches to improve the success of structure determination of membrane proteins. Following a broad screen of sequence space to identify initial expression-positive targets, we employ a second step to select orthologs with closely related sequences to these hits. We demonstrate that a greater percentage of these latter targets express well and are stable in detergent, increasing the likelihood of identifying candidates that will ultimately yield structural information.

Keywords: high throughput biology; integral membrane proteins; protein expression; protein purification; structural biology; structural genomics.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Bacteria / genetics
  • Bacteria / metabolism*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Genomics
  • Membrane Proteins / chemistry*
  • Membrane Proteins / genetics*
  • Models, Molecular
  • Protein Conformation

Substances

  • Bacterial Proteins
  • Membrane Proteins