A survey of integral a-helical membrane proteins

Abstract Membrane proteins serve as cellular gatekeep-ers, 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-asso-ciated 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 con-tent and evolutionary associations between membrane proteins and families in a diverse set of genomes is lacking. Here, a membrane protein annotation pipeline was devel-oped to define the integral membrane genome and associ-ations 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. Fur-thermore, the methodology was applied (1) to explore the evolutionary history of the substrate-binding transmem-brane domains of the human ABC transporter superfamily, (2) to identify the multidrug resistance-associated mem-brane proteins in whole genomes, and (3) to identify putative new membrane protein families