Practice question

ABC transporter superfamily represents large gene family with 48 members in humans associated with inherited disorders and drug resistance, present also in bacteria where many function as importers. Core architecture comprises two transmembrane domains typically six helices each forming substrate translocation chamber with diverse selectivity filters, and two nucleotide binding domains located cytoplasmically containing Walker A phosphate binding P-loop, Walker B magnesium coordination hhhhhD, signature C motif LSGGQ characteristic of ABC plus H-loop and Q-loop coordinating ATP. Transport cycle involves ATP binding inducing tight dimerization of nucleotide binding domains sandwiching nucleotides, converting transmembrane domains from inward to outward facing releasing substrate, ATP hydrolysis and ADP plus phosphate release resetting to inward. This mechanism promiscuous for chemically diverse substrates: anionic chloride via CFTR, cationic lipids cholesterol via ABCA1 contributing to HDL formation, phosphatidylcholine via ABCB4, bile salts via ABCB11, peptides via TAP for MHC class I presentation, and myriad hydrophobic drugs including vinca alkaloids, anthracyclines exported by P-glycoprotein MDR1 conferring multidrug resistance in cancer and bacterial antibiotic resistance. Therefore transport of lipophilic molecules and multidrug resistance exemplifies family function.