STRUCTURES AND REACTION MECHANISMS OF ABC TRANSPORTERS

摘要

My view of the present state of research on the structure and mechanism of ATP-binding cassette (ABC) transporters ABC transporters are primary active transporters that have an important role in the physiology and pathophysiology of many organisms. Fueled by hydrolysis of ATP, these proteins allow nutrients, metabolites, and noxious substances to be moved across lipid bilayers [1]. In bacteria, ABC importers facilitate the uptake of nutrients from the environment via high-affinity uptake pathways, thus enabling pathogenic bacteria to acquire essential (micro-)nutrients even when they are scarce. ABC exporters catalyze the extrusion of components required for the biosynthesis of the bacterial cell envelope and often contribute to drug resistance, which can pose problems in combatting pathogenic bacteria. In eukaryotes, ABC transporters are generally exporters that move diverse substrates across cellular or organelle membranes. Various hereditary human diseases have been associated with the dysfunction of ABC transporters, and their over-expression in tumor cells can cause multi-drug resistance, a serious impediment for the treatment of cancer [2]. A great deal of progress has been made over the past 15 years in the structural and mechanistic investigation of ABC transporters. Specifically, X-ray crystallo-graphic studies have revealed their folds and have visualized distinct conformations. The structural insight was useful for interpreting functional, biophysical, and biochemical studies and proved invaluable in understanding the coupling mechanisms of several model systems. While the first structures described ABC transporters of bacterial or archaeal origin, advances in over-expression and purification of eukaryotic membrane proteins have allowed the mechanisms of ABC transporters related to human diseases to be tackled.