title: A survey of integral alpha-helical membrane proteins.
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.
authors.affiliation: Graduate Group in Bioinformatics, University of California at San Francisco, San Francisco, CA, USA. libusha@salilab.org
authors.forename: Libusha
authors.initials: L
authors.lastname: Kelly
authors.forename: Ursula
authors.initials: U
authors.lastname: Pieper
authors.forename: Narayanan
authors.initials: N
authors.lastname: Eswar
authors.forename: Franklin A
authors.initials: FA
authors.lastname: Hays
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Zygy
authors.initials: Z
authors.lastname: Roe-Zurz
authors.forename: Deanna L
authors.initials: DL
authors.lastname: Kroetz
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Giacomini
authors.forename: Robert M
authors.initials: RM
authors.lastname: Stroud
authors.forename: Andrej
authors.initials: A
authors.lastname: Sali
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000818:Animals; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019143:Evolution, Molecular; D015894:Genome, Human / Q000235:genetics*; D023281:Genomics / Q000379:methods; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D017433:Protein Structure, Secondary / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*
chemical_list: D018528:ATP-Binding Cassette Transporters; D008565:Membrane Proteins; D043562:Receptors, G-Protein-Coupled