Purification and crystallisation of the cystic fibrosis transmembrane conductance regulator (CFTR)

Mark F. Rosenberg, Alhaji Bukar Kamis, Luba A. Aleksandrov, Robert C. Ford, John R. Riordan

    Research output: Contribution to journalArticlepeer-review

    Abstract

    The cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane protein that is mutated in patients suffering from cystic fibrosis. Here we report the purification and first crystallization of wild-type human CFTR. Functional characterization of the material showed it to be highly active. Electron crystallography of negatively stained two-dimensional crystals of CFTR has revealed the overall architecture of this channel for two different conformational states. These show a strong structural homology to two conformational states of another eukaryotic ATP-binding cassette transporter, P-glycoprotein. In contrast to P-glycoprotein, however, both conformational states can be observed in the presence of a nucleotide, which may be related to the role of CFTR as an ion channel rather than a transporter. The hypothesis that the two conformations could represent the "open" and "closed" states of the channel is considered.
    Original languageEnglish
    Pages (from-to)39051-39057
    Number of pages6
    JournalJournal of Biological Chemistry
    Volume279
    Issue number37
    DOIs
    Publication statusPublished - 10 Sept 2004

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