Abstract 95: Phylogenetic Classification, Structural Evolution, and Functional Divergence of the ABC-type Transporters: Inferences Derived from CDTree/Cn3D Software Applications

Abstract The NCBI's Conserved Domain Database (CDD; http://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml), is a collection of annotated multiple sequence alignment models representing ancient conserved protein domains, basic units of protein function and protein evolution. Domain models are annotated with functional sites and can be viewed as sequence alignments together with corresponding 3D structure using the CDTree/Cn3D software applications. CDTree/Cn3D is a domain hierarchy editor which lets the user view and examine conserved domain hierarchies interactively and in great detail. A domain hierarchy is a structured collection of domain models reflecting the domain family's molecular evolution. Here we present our current, functionally annotated evolutionary classifications of the nucleotide-binding domain, transmembrane domain, and periplasmic binding proteins of the ABC (ATP binding cassette)-type transport systems which are involved in the transport of a wide variety of substrates such as sugars, ions, peptides, and more complex organic molecules across membranes. Mutations in ABC transporters cause or contribute to multi-drug resistance, cystic fibrosis, and a range of other human diseases. Using CDTree/Cn3D functionality, subfamilies present in diverse organisms were inferred from the multiple sequence alignments, phylogenetic trees, and the domain architectures of the proteins involved. Furthermore subfamilies, some of which are only comprised of uncharacterized proteins, were annotated with molecular and cellular function and the location of conserved sites, as available in the literature and evident from protein 3D structure. We demonstrate the utility of CDTree/Cn3D in studying the molecular evolution of protein and domain families, and in accelerating the discovery of orthologous groups. CDTree/Cn3D are freely available for download via the CDD website. A version of CDTree, which supports both Mac OSX and Windows operating systems, has recently been made available. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 95.