Cellular and Molecular Life Sciences CMLS

, Volume 61, Issue 2, pp 230–242

Nucleotide-binding domains of human cystic fibrosis transmembrane conductance regulator: detailed sequence analysis and three-dimensional modeling of the heterodimer

Research Article

DOI: 10.1007/s00018-003-3386-z

Cite this article as:
Callebaut, I., Eudes, R., Mornon, JP. et al. CMLS, Cell. Mol. Life Sci. (2004) 61: 230. doi:10.1007/s00018-003-3386-z

Abstract

The cystic fibrosis transmembrane conductance regulator (CFTR) protein is encoded by the gene that is defective in cystic fibrosis, the most common lethal inherited disease among the Caucasian population. CFTR belongs to the ABC transporter superfamily, whose members form macromolecular architectures composed of two membrane-spanning domains and two nucleotide-binding domains (NBDs). The experimental structures of NBDs from several ABC transporters have recently been solved, opening new avenues for understanding the structure/function relationships and the consequences of some disease-causing mutations of CFTR. Based on a detailed sequence/structure analysis, we propose here a three-dimensional model of the human CFTR NBD heterodimer. This model, which is in agreement with recent experimental data, highlights the specific features of the CFTR asymmetric active sites located at the interface between the two NBDs. Moreover, additional CFTR-specific features can be identified at the subunit interface, which may play critical roles in active site interdependence and are uncommon in other NBD dimers.

ABC transportercystic fibrosisCFTRMRP1SUR1disease-causing mutationmolecular modelinghydrophobic cluster analysis

Copyright information

© Birkhäuser-Verlag Basel 2004

Authors and Affiliations

  1. 1.Systèmes moléculaires & Biologie structurale, LMCP, CNRS UMR7590Universités Paris 6 & Paris 7ParisFrance
  2. 2.INSERM U458Hôpital Robert DebréParisFrance