title: The cytoplasmic domain of the chloride channel ClC-0: structural and dynamic characterization of flexible regions.
abstract: Eukaryotic members of the ClC family of chloride channels and transporters are composed of a transmembrane ion transport domain followed by a cytoplasmic domain, which is believed to be involved in the modulation of ClC function. In some family members this putative regulatory domain contains next to a well-folded structured part, long sequence stretches with low sequence complexity. These regions, a 96 residue long linker connecting two structured sub-domains, and 35 residues on the C teminus of the domain were found disordered in a recent crystal structure of this domain in ClC-0. Both regions have a large influence on the modulation of channel function in closely related family members. Here we describe a NMR study to characterize the structural and dynamic properties of these putatively unstructured stretches. Our study reveals that the two regions indeed show large conformational flexibility with dynamics on the nanosecond timescale. However, small islands of secondary structure are found interdispersed between the unfolded regions. This study characterizes for the first time the biophysical properties of these protein segments, which may become important for the understanding of novel regulatory mechanisms within the ClC family.
authors.affiliation: Laboratorium für Physikalische Chemie, ETH Zürich, CH-8093 Zürich, Switzerland.
authors.forename: Simon
authors.initials: S
authors.lastname: Alioth
authors.forename: Sebastian
authors.initials: S
authors.lastname: Meyer
authors.forename: Raimund
authors.initials: R
authors.lastname: Dutzler
authors.forename: Konstantin
authors.initials: K
authors.lastname: Pervushin
mesh_terms: D000595:Amino Acid Sequence; D018118:Chloride Channels / Q000737:chemistry* / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017434:Protein Structure, Tertiary
chemical_list: D018118:Chloride Channels