Ratiocinative screen of eukaryotic integral membrane protein expression and solubilization for structure determination

J Struct Funct Genomics. 2009 Mar;10(1):9-16. doi: 10.1007/s10969-008-9046-7. Epub 2008 Nov 22.


Persistent hurdles impede the successful determination of high-resolution crystal structures of eukaryotic integral membrane proteins (IMP). We designed a high-throughput structural genomics oriented pipeline that seeks to minimize effort in uncovering high-quality, responsive non-redundant targets for crystallization. This "discovery-oriented" pipeline sidesteps two significant bottlenecks in the IMP structure determination pipeline: expression and membrane extraction with detergent. In addition, proteins that enter the pipeline are then rapidly vetted by their presence in the included volume on a size-exclusion column--a hallmark of well-behaved IMP targets. A screen of 384 rationally selected eukaryotic IMPs in baker's yeast Saccharomyces cerevisiae is outlined to demonstrate the results expected when applying this discovery-oriented pipeline to whole-organism membrane proteomes.

Publication types

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

MeSH terms

  • Animals
  • Crystallography, X-Ray
  • Databases, Protein
  • Genomics
  • Humans
  • Membrane Proteins / chemistry*
  • Protein Conformation
  • Proteome / analysis
  • Saccharomyces cerevisiae Proteins / metabolism


  • Membrane Proteins
  • Proteome
  • Saccharomyces cerevisiae Proteins