Structural and functional diversity calls for a new classification of ABC transporters
Christoph Thomas, Stephen G. Aller, Konstantinos Beis, Elisabeth P. Carpenter, Geoffrey Chang, Lei Chen, Elie Dassa, Michael Dean, Franck Duong, Damian C. Ekiert, Robert C. Ford, Rachelle Gaudet, Xin Gong, I. Barry Holland, Yihua Huang, Daniel K. Kahne, Hiroaki Kato, Vassilis Koronakis, Christopher M. Koth, Youngsook Lee, Oded Lewinson, Roland Lill, Enrico Martinoia, Satoshi Murakami, Heather W. Pinkett, Bert Poolman, Daniel M. Rosenbaum, Balázs Sarkadi, Lutz Schmitt, Erwin Schneider, Yigong Shi, Show‐Ling Shyng, Dirk Jan Slotboom, Emad Tajkhorshid, D. Peter Tieleman, Kazumitsu Ueda, András Váradi, Po‐Chao Wen, Nieng Yan, Peng Zhang, Hongjin Zheng, Jochen Zimmer, Robert Tampé
Abstract
Members of the ATP-binding cassette (ABC) transporter superfamily translocate a broad spectrum of chemically diverse substrates. While their eponymous ATP-binding cassette in the nucleotide-binding domains (NBDs) is highly conserved, their transmembrane domains (TMDs) forming the translocation pathway exhibit distinct folds and topologies, suggesting that during evolution the ancient motor domains were combined with different transmembrane mechanical systems to orchestrate a variety of cellular processes. In recent years, it has become increasingly evident that the distinct TMD folds are best suited to categorize the multitude of ABC transporters. We therefore propose a new ABC transporter classification that is based on structural homology in the TMDs.