Topological Model Of Membrane Domain Of The Cystic Fibrosis Transmembrane Conductance Regulator

[en] The cystic fibrosis transmembrane conductance regulator is a cAMP-regulated chloride channel. We used molecular modelling to predict 3-D models for the CFTR membrane domain. Hydropathy and residue conservation in all CFTRs as well as in other proteins suggested that the membrane domain is a 12-helix bundle. If the domain is enclosing a channel for chloride, it could be made of five helices. We propose two structural models in which both lumenal and cytoplasmic entrances to the chloride pore have a ring of positively charged residues. The inner surface of the channel is covered with neutral polar plus one or two charged residues. Helices that are not directly involved in the chloride channel could organise to form a second channel; a dimeric symmetrical structure is proposed. Analysis raised interest for helix 5: this hydrophobic fragment is conserved in all CFTRs and aligns with segments present in several different ion channels and transporters. The existence of an FFXXFFXXF motif is proposed. Helix 5 could be an important domain of CFTRs. The models agree with available data from pathological mutations but does not account for the membrane insertion of a hydrophilic fragment of NBDI.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Gallet, X.

Festy, F.

Ducarme, P.

Brasseur, Robert ; Université de Liège - ULiège > Gembloux Agro-Bio Tech

Thomas, Annick ; Université de Liège - ULiège > Chimie et bio-industries > Centre de Bio. Fond. - Section de Biologie moléc. et numér.

Language :

English

Title :

Topological Model Of Membrane Domain Of The Cystic Fibrosis Transmembrane Conductance Regulator

Publication date :

1998

Journal title :

Journal of Molecular Graphics and Modelling

ISSN :

1093-3263

eISSN :

1873-4243

Publisher :

Elsevier, Netherlands

Volume :

Issue :

Pages :

72-+
97-8

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 25 June 2010

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