Article

Journal of Structural and Functional Genomics

, 10:269

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

A survey of integral α-helical membrane proteins

  • Libusha KellyAffiliated withGraduate Group in Bioinformatics, University of California at San FranciscoDepartment of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, and California Institute for Quantitative Biosciences, University of California at San Francisco Email author 
  • , Ursula PieperAffiliated withDepartment of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, and California Institute for Quantitative Biosciences, University of California at San Francisco
  • , Narayanan EswarAffiliated withDepartment of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, and California Institute for Quantitative Biosciences, University of California at San Francisco
  • , Franklin A. HaysAffiliated withDepartment of Biochemistry and Biophysics, University of California at San Francisco
  • , Min LiAffiliated withMembrane Protein Expression Center, University of California at San Francisco
  • , Zygy Roe-ZurzAffiliated withMembrane Protein Expression Center, University of California at San Francisco
  • , Deanna L. KroetzAffiliated withDepartment of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, and California Institute for Quantitative Biosciences, University of California at San Francisco
  • , Kathleen M. GiacominiAffiliated withDepartment of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, and California Institute for Quantitative Biosciences, University of California at San Francisco
  • , Robert M. StroudAffiliated withMembrane Protein Expression Center, University of California at San FranciscoDepartment of Biochemistry and Biophysics, University of California at San FranciscoCenter for the Structure of Membrane Proteins, University of California at San Francisco
    • , Andrej SaliAffiliated withDepartment of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, and California Institute for Quantitative Biosciences, University of California at San Francisco Email author 

Abstract

Membrane proteins serve as cellular gatekeepers, regulators, and sensors. Prior studies have explored the functional breadth and evolution of proteins and families of particular interest, such as the diversity of transport-associated membrane protein families in prokaryotes and eukaryotes, the composition of integral membrane proteins, and family classification of all human G-protein coupled receptors. However, a comprehensive analysis of the content and evolutionary associations between membrane proteins and families in a diverse set of genomes is lacking. Here, a membrane protein annotation pipeline was developed to define the integral membrane genome and associations between 21,379 proteins from 34 genomes; most, but not all of these proteins belong to 598 defined families. The pipeline was used to provide target input for a structural genomics project that successfully cloned, expressed, and purified 61 of our first 96 selected targets in yeast. Furthermore, the methodology was applied (1) to explore the evolutionary history of the substrate-binding transmembrane domains of the human ABC transporter superfamily, (2) to identify the multidrug resistance-associated membrane proteins in whole genomes, and (3) to identify putative new membrane protein families.

Keywords

Membrane proteins Superfamily analysis Multidrug resistance ABC transporters Target selection