Tracing the structural evolution of eukaryotic ATP binding cassette transporter superfamily.

Jie Xiong,Jinmei Feng,Jun Zhou,Wei Miao,Dongxia Yuan

doi:10.1038/srep16724

Abstract

The ATP binding cassette (ABC) transporters superfamily is one of the largest classes of membrane proteins. The core of the ABC transporter protein is composed of transmembrane domains (TMDs) and nucleotide binding domains (NBD). Eukaryotes ABC transporters are classified into seven main families (ABCA to ABCG) based on sequence similarity and domain organizations. With different domain number and domain organizations, eukaryote ABC transporters show diverse structures: the single structure (NBD or TMD), the ABC2 structure (NBD-NBD), the half structure (TMD-NBD or NBD-TMD) and the full structure (TMD-NBD-TMD-NBD or NBD-TMD-NBD-TMD). However, studies on how various ABC transporter gene structures evolved is still absent. Therefore, in this study, we comprehensively investigated the structural evolution of eukaryotic ABC transporters. The seven eukaryote ABC transporter families (A to G) fell into three groups: A&G group, B,C&D group and E&F group. There were at least four times the number of NBD and TMD fusion events in the origin of the half structure transporter. Two fusion modes were found in the full and ABC2 structure origination. Based on these findings, we present a putative structural evolutionary path of eukaryote ABC transporters that will increase our understanding on their origin, divergence and function.

Highlights

The movement of molecules into and out of cells is mediated by cell membranes, in many cases by specialized membrane proteins known as transporters
A single transmembrane domain (TMD) and nucleotide binding domain (NBD) can be fused to a half structure transporter, two different NBDs can be fused to the ABC2 structure, and two half structure transporters could be fused to the full structure transporter
One of the four half structure transporters diverged into ABCC N-terminal, C-terminal and ABCB half structure transporters

Summary

Introduction

The movement of molecules into and out of cells is mediated by cell membranes, in many cases by specialized membrane proteins known as transporters. A typical structure of eukaryotic ABC transporters consists of two conserved domains: a transmembrane domain (TMD) and a nucleotide binding domain (NBD)[3]. In non-transporter ABC proteins, only NBDs are present at both the N- and the C-terminus. Such cases with NBD-NBD organization is referred to as the ABC2 structure. One study investigated ABC transporters in 20 model organisms with the objective of identifying the function of proteins based on sequence similarity using a simple method known as the “function transfer rule”[20]. We investigated the phylogeny of the ABC transporter superfamily using proteins from diverse eukaryote kingdoms, analyzed domain features, and proposed a detailed path that traces the evolution of the diverse structures of the ABC transporter superfamily

Methods

Results

Discussion

Conclusion