title: Functional Monomerization of a ClC-Type Fluoride Transporter.
abstract: Anion channels and antiporters of the ClC superfamily have been found to be exclusively dimeric in nature, even though each individual monomer contains the complete transport pathway. Here, we describe the destabilization through mutagenesis of the dimer interface of a bacterial F(-)/H(+) antiporter, ClC(F)-eca. Several mutations that produce monomer/dimer equilibrium of the normally dimeric transporter were found, simply by shortening a hydrophobic side chain in some cases. One mutation, L376W, leads to a wholly monomeric variant that shows full activity. Furthermore, we discovered a naturally destabilized homologue, ClC(F)-rla, which undergoes partial monomerization in detergent without additional mutations. These results, in combination with the previous functional monomerization of the distant relative ClC-ec1, demonstrate that the monomer alone is the functional unit for several clades of the ClC superfamily.
authors.affiliation: Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, MA 02454, USA.
authors.forename: Nicholas B
authors.initials: NB
authors.lastname: Last
authors.affiliation: Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, MA 02454, USA. Electronic address: cmiller@brandeis.edu.
authors.forename: Christopher
authors.initials: C
authors.lastname: Miller
mesh_terms: D000595:Amino Acid Sequence; D017920:Antiporters / Q000737:chemistry / Q000378:metabolism*; D018118:Chloride Channels / Q000737:chemistry* / Q000378:metabolism; D002712:Chlorides / Q000737:chemistry / Q000378:metabolism*; D016983:Enterococcus / Q000378:metabolism*; D005459:Fluorides / Q000737:chemistry / Q000378:metabolism*; D017136:Ion Transport; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010710:Phosphates / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D017920:Antiporters; D018118:Chloride Channels; D002712:Chlorides; D026901:Membrane Transport Proteins; D010710:Phosphates; C012980:fluorophosphate; D005459:Fluorides
keywords: antiporter; membrane protein; protein oligomerization; transmembrane interactions