Basis of substrate binding and conservation of selectivity in the CLC family of channels and transporters

Alessandra Picollo; Mattia Malvezzi; Jon Houtman; Alessio Accardi

doi:10.1038/nsmb.1704

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Basis of substrate binding and conservation of selectivity in the CLC family of channels and transporters

Journal article

Peer reviewed

Basis of substrate binding and conservation of selectivity in the CLC family of channels and transporters

Alessandra Picollo, Mattia Malvezzi, Jon Houtman and Alessio Accardi

Nature structural & molecular biology, Vol.16(12), pp.1294-1301

12/2009

DOI: 10.1038/nsmb.1704

PMCID: PMC2920496

PMID: 19898476

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Abstract

Ion binding to secondary active transporters triggers a cascade of conformational rearrangements resulting in substrate translocation across cellular membranes. Despite the fundamental role of this step, direct measurements of binding to transporters are rare. We investigated ion binding and selectivity in CLC-ec1, a H + /Cl − exchanger of the CLC family of channels and transporters. Cl − affinity depends on the conformation of the protein: it is highest with the extracellular gate removed, and weakens as the transporter adopts the occluded configuration and with the intracellular gate removed. The central ion-binding site determines selectivity in CLC transporters and channels, a serine to proline substitution at this site confers NO 3 − selectivity upon the Cl − specific CLC-ec1 transporter and CLC-0 channel. We propose that CLC-ec1 operates through an affinity-switch mechanism and that the bases of substrate specificity are conserved in the CLC channels and transporters.

channel

chloride

Isothermal titration calorimetry

transport

Details

Title: Subtitle: Basis of substrate binding and conservation of selectivity in the CLC family of channels and transporters
Creators: Alessandra Picollo - Department of Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242
Mattia Malvezzi - Department of Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242
Jon Houtman - Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242
Alessio Accardi - Department of Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242
Resource Type: Journal article
Publication Details: Nature structural & molecular biology, Vol.16(12), pp.1294-1301
DOI: 10.1038/nsmb.1704
PMID: 19898476
PMCID: PMC2920496
NLM abbreviation: Nat Struct Mol Biol
ISSN: 1545-9993
eISSN: 1545-9985
Language: English
Date published: 12/2009
Academic Unit: Microbiology and Immunology; Internal Medicine
Record Identifier: 9984094312102771

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