Building an understanding of cystic fibrosis on the foundation of ABC transporter structures

Juan L. Mendoza, Philip J. Thomas

Research output: Contribution to journalReview article

37 Scopus citations

Abstract

Cystic fibrosis (CF) is a fatal disease affecting the lungs and digestive system by impairment of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). While over 1000 mutations in CFTR have been associated with CF, the majority of cases are linked to the deletion of phenylalanine 508 (ΔF508). F508 is located in the first nucleotide binding domain (NBD1) of CFTR. This mutation is sufficient to impair the trafficking of CFTR to the plasma membrane and, thus, its function. As an ABC transporter, recent structural data from the family provide a framework on which to consider the effect of the ΔF508 mutation on CFTR. There are fifty-seven known structures of ABC transporters and domains thereof. Only six of these structures are of the intact transporters. In addition, modern bioinformatic tools provide a wealth of sequence and structural information on the family. We will review the structural information from the RCSB structure repository and sequence databases of the ABC transporters. The available structural information was used to construct a model for CFTR based on the ABC transporter homologue, Sav1866, and provide a context for understanding the molecular pathology of Cystic Fibrosis.

Original languageEnglish (US)
Pages (from-to)499-505
Number of pages7
JournalJournal of Bioenergetics and Biomembranes
Volume39
Issue number5-6
DOIs
StatePublished - Dec 1 2007

Keywords

  • ABC transporters
  • CFTR
  • Cystic fibrosis

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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