Linker Domains: Why ABC Transporters 'Live in Fragments no Longer'

Abstract

ATP-binding cassette (ABC) transporters are membrane proteins present in all kingdoms of life. We have considered the disordered region that connects the N- and C-terminal halves in many eukaryotic ABC transporters, allowing all four consensus functional domains to be linked. The recent availability of structures of ABC transporters containing linker regions has allowed us to identify the start and end points of the connectors as well as hinting at their localisation. We address questions such as: Where did the linker regions come from? Why do some ABC transporters have connectors and others not? What are the rules and roles of the linker regions? What are the consequences of mutations in these connector regions for disease in humans?

Keywords: ABC transporters; domain linker; evolution; regulation; structure–function relationship.