Is the emperor wearing shorts? The published structures of ABC transporters

ABC transporters use the energy of ATP binding and hydrolysis to transport substrates across cellular membranes. They comprise two highly conserved nucleotide binding domains and two transmembrane domains that form the transmembrane channel and contain the substrate binding sites. Structural analyses have found a variety of seemingly unrelated folds for the ABC transporter transmembrane domains, and from these, a set of diverse mechanistic models has been inferred. Nevertheless, in spite of the explosion in structure determination of ABC transporters in the last decade, advancement in certainty and clarity as to fundamental aspects of their molecular mechanisms remains elusive. With this in mind, here we put and examine the question: Could current ABC structures differ from the physiologic membrane-embedded forms?