Models of the transmembrane domains of the yeast mitochondrial citrate transport protein

We have used cysteine scanning, hydropathy analysis and molecular modeling to construct four possible models of the transmembrane helical domains of t he yeast mitochondrial citrate transport protein. Models 1 and 2 invoke the formation of a translocation pathway by the six membrane-spanning alpha-he lical domains that comprise each citrate transport protein monomer. Thus th e homodimeric CTP (the functional form of the CTP) would contain two separa te translocation pathways. Models 3 and 4 explore a novel way in which dime rization might take place, in which transmembrane domain 3 would form part of the dimer interface. This would lead to the formation of two seven-helix translocation pathways within the transporter dimer. Importantly, these st udies have led to the construction of the first detailed structural models for any of the mitochondrial anion transport proteins, a family of proteins which is essential to cellular bioenergetics. Furthermore, these models su ggest numerous experiments which can be carried out to further elucidate th e structure of the translocation pathway through the membrane.