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| Subject Categories: Membranes & Transport | Structural Biology |
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| The EMBO Journal
(2006) 25, 3762–3773, doi:10.1038/sj.emboj.7601269 Published online 10 August 2006 |
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| A structural basis for Mg2+ homeostasis and the CorA translocation cycle |
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| Jian Payandeh1, 2 and Emil F Pai1, 2, 3, 4 |
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1 Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada 2 Division of Cancer Genomics & Proteomics, Ontario Cancer Institute, MaRS Centre, Toronto Medical Discovery Tower, Toronto, Ontario, Canada 3 Department of Biochemistry, University of Toronto, Ontario, Canada 4 Department of Molecular & Medical Genetics, University of Toronto, Toronto, Ontario, Canada To whom correspondence should be addressed Jian Payandeh, Division of Cancer Genomics & Proteomics, Ontario Cancer Institute, MaRS Centre, Toronto Medical Discovery Tower, 101 College Street, Toronto, Ontario, Canada M5G 1L7. Tel.: 416 581 7545; Fax: 416 581 7545; E-mail: payandeh@uhnres.utoronto.ca or pai@hera.med.utoronto.ca Emil F Pai, Division of Cancer Genomics & Proteomics, Ontario Cancer Institute, MaRS Centre, Toronto Medical Discovery Tower, 101 College Street, Toronto, Ontario, Canada M5G 1L7. Tel.: 416 581 7545; Fax: 416 581 7545; E-mail: payandeh@uhnres.utoronto.ca or pai@hera.med.utoronto.ca Received 12 May 2006; Accepted 13 July 2006; Published online 10 August 2006. |
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| Abstract |
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We describe the CorA Mg2+ transporter homologue from Thermotoga maritima in complex with 12 divalent cations at 3.7 Å resolution. One metal is found near the universally conserved GMN motif, apparently stabilized within the transmembrane region. This portion of the selectivity filter might discriminate between the size and preferred coordination geometry of hydrated substrates. CorA may further achieve specificity by requiring the sequential dehydration of substrates along the length of its  55 Å long pore. Ten metal sites identified within the cytoplasmic funnel domain are linked to long extensions of the pore helices and regulate the transport status of CorA. We have characterized this region as an intrinsic divalent cation sensor and provide evidence that it functions as a Mg2+-specific homeostatic molecular switch. A proteolytic protection assay, biophysical data, and comparison to a soluble domain structure from Archaeoglobus fulgidus have revealed the potential reaction coordinate for this diverse family of transport proteins. |
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| Keywords: magnesium homeostasis and transport, open state model, selectivity filter, translocation cycle, X-ray crystallography |
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