Selected Discussion Topic Answers

• Cystic Fibrosis:
  • What is the major metabolic defect in this disease?
    • There is a mutation damaging the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride ion channel. This mutation results in an excess concentration of chloride and sodium in sweat and other fluids. The result is a buildup of mucus etc. making breathing difficult.
  • What are "ABC's" and "NBD's"? What is their relationship to each other?
    • ABCs are are ATP-binding cassettes containing two nucleotide (ATP) binding domains (NDBs). All bind and hydrolze ATP.
    • NDBs are nucleotide-binding protein domains. They bind and hydrolyze ATP.
  • How do the NBD engines seem to convert ATP energy into membrane transport?
    • ATP hydrolysis catalyzed by the NDB domain results in a change in conformation of the ATP-binding cassette. The conformational change is in turn trasmitted to membrane-spanning domains (MSDs) which result in a variety of activities, depending on the particular membrane protein (e.g. ion-pumping, ion conductance, regulation of other membrane proteins).
  • What are G proteins? What is their relationship to the ABC transporters.
    • G-proteins are guanine nucleotide binding proteins which use the exchange of GDP for GTP in activating/regulating second messenger cascades.
    • G-proteins have similar confrmations and actions to the ABC transporters.They share short regions of sequence similarity (Walker A motif or Phosphate binding loop and a Walker B motif with a conserved aspartate residue).

Last modified 3 April 2013