Department of Anesthesiology

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Structure and gating of CLC channels and exchangers.

TitleStructure and gating of CLC channels and exchangers.
Publication TypeJournal Article
Year of Publication2015
AuthorsAccardi A
JournalJ Physiol
Volume593
Issue18
Pagination4129-38
Date Published2015 Sep 15
ISSN1469-7793
Abstract

Since their serendipitous discovery the CLC family of Cl(-) transporting proteins has been a never ending source of surprises. From their double-barrelled architecture to their complex structure and divergence as channels and transporters, the CLCs never cease to amaze biophysicists, biochemists and physiologists alike. These unusual functional properties allow the CLCs to fill diverse physiological niches, regulating processes that range from muscle contraction to acidification of intracellular organelles, nutrient accumulation and survival of bacteria to environmental stresses. Over the last 15 years, the availability of atomic-level information on the structure of the CLCs, coupled to the discovery that the family is divided into passive channels and secondary active transporters, has revolutionized our understanding of their function. These breakthroughs led to the identification of the key structural elements regulating gating, transport, selectivity and regulation by ligands. Unexpectedly, many lines of evidence indicate that the CLC exchangers function according to a non-conventional transport mechanism that defies the fundamental tenets of the alternating-access paradigm for exchange transport, paving the way for future unexpected insights into the principles underlying active transport and channel gating.

DOI10.1113/JP270575
Alternate JournalJ. Physiol. (Lond.)
PubMed ID26148215
PubMed Central IDPMC4594288