Mg
            <sup>2+</sup>
            -sensing mechanism of Mg
            <sup>2+</sup>
            transporter MgtE probed by molecular dynamics study

Ishitani, Ryuichiro; Sugita, Yuji; Dohmae, Naoshi; Furuya, Noritaka; Hattori, Motoyuki; Nureki, Osamu

doi:10.1073/pnas.0802991105

Cited by 56 publications

(62 citation statements)

References 29 publications

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“…Four putative Mg 2ϩ ions are bound at the interface of the connecting helices and the TMD and CBS domains and stabilize the closed state of the pore. Without Mg 2ϩ (low intracellular concentrations), the CBS2 domains are repelled from each other by the negatively charged residues at the dimer interface, which favors the open conformation (30,31). Overall, these findings support the idea that the tandem CBS domains sense intracellular ligands and elicit conformational changes in the associated protein domains.…”

Section: Discussionsupporting

confidence: 75%

“…and the functions of the CBS domains. CBS domains have been found associated with ABC transporters (12,53), chloride channels of the CLC family (54 -58), magnesium transporters (30,31), and water-soluble enzymes, including sugar (D-arabinose 5-phosphate) isomerases (59), AMP-activated protein kinase (60 -63), inosine 5Ј-monophosphate dehydrogenase (60,61,64), metalloproteases (65), pyrophosphatases (29), and many proteins with unknown functions.…”

Section: Discussionmentioning

confidence: 99%

“…CBS domains are not highly conserved in sequence, and the molecular basis for regulation by CBS is poorly understood, although over 30,000 CBS-containing proteins are known to date. In some cases, conformational changes at the CBS dimer interface have been reported upon the binding of nucleotides (28,29) or Mg 2ϩ ions (30,31).…”

mentioning

confidence: 99%

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Cystathionine β-Synthase (CBS) Domains 1 and 2 Fulfill Different Roles in Ionic Strength Sensing of the ATP-binding Cassette (ABC) Transporter OpuA

Karasawa

Erkens

Berntsson

et al. 2011

Journal of Biological Chemistry

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The cystathionine ␤-synthase module of OpuA in conjunction with an anionic membrane surface acts as a sensor of internal ionic strength, which allows the protein to respond to osmotic stress. We now show by chemical modification and cross-linking studies that CBS2-CBS2 interface residues are critical for transport activity and/or ionic regulation of transport, whereas CBS1 serves no functional role. We establish that Cys residues in CBS1, CBS2, and the nucleotide-binding domain are more accessible for cross-linking at high than low ionic strength, indicating that these domains undergo conformational changes when transiting between the active and inactive state. Structural analyses suggest that the cystathionine ␤-synthase module is largely unstructured. Moreover, we could substitute CBS1 by a linker and preserve ionic regulation of transport. These data suggest that CBS1 serves as a linker and the structured CBS2-CBS2 interface forms a hinge point for ionic strength-dependent rearrangements that are transmitted to the nucleotide-binding domain and thereby affect translocation activity.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

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Cystathionine β-Synthase (CBS) Domains 1 and 2 Fulfill Different Roles in Ionic Strength Sensing of the ATP-binding Cassette (ABC) Transporter OpuA

Karasawa

Erkens

Berntsson

et al. 2011

Journal of Biological Chemistry

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“…Crystal structures of four unrelated proteins have demonstrated that ligand interactions induce relatively large-scale changes in Bateman domain dimer conformations (22,(44)(45)(46). For example, Mg 2þ binding to the Bateman domain dimer of the bacterial channel Mg 2þ MgtE induces an open-to-closed conformational change by shielding the charge-charge repulsion of acidic amino acid residues (22,45,47).…”

Section: Discussionmentioning

confidence: 99%

“…For example, Mg 2þ binding to the Bateman domain dimer of the bacterial channel Mg 2þ MgtE induces an open-to-closed conformational change by shielding the charge-charge repulsion of acidic amino acid residues (22,45,47). By analogy with MgtE, binding and unbinding Values are means 5 SE (n).…”

Section: Discussionmentioning

confidence: 99%

Role of CBS and Bateman Domains in Phosphorylation-Dependent Regulation of a CLC Anion Channel

Yamada

Krzeminski

Bozóky

et al. 2016

Biophysical Journal

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Eukaryotic CLC anion channels and transporters are homodimeric proteins composed of multiple a-helical membrane domains and large cytoplasmic C-termini containing two cystathionine-b-synthase domains (CBS1 and CBS2) that dimerize to form a Bateman domain. The Bateman domains of adjacent CLC subunits interact to form a Bateman domain dimer. The functions of CLC CBS and Bateman domains are poorly understood. We utilized the Caenorhabditis elegans CLC-1/2/Ka/ Kb anion channel homolog CLH-3b to characterize the regulatory roles of CLC cytoplasmic domains. CLH-3b activity is reduced by phosphorylation or deletion of a 14-amino-acid activation domain (AD) located on the linker connecting CBS1 and CBS2. We demonstrate here that phosphorylation-dependent reductions in channel activity require an intact Bateman domain dimer and concomitant phosphorylation or deletion of both ADs. Regulation of a CLH-3b AD deletion mutant is reconstituted by intracellular perfusion with recombinant 14-amino-acid AD peptides. The sulfhydryl reactive reagent 2-(trimethylammonium)ethyl methanethiosulfonate bromide (MTSET) alters in a phosphorylation-dependent manner the activity of channels containing single cysteine residues that are engineered into the short intracellular loop connecting membrane a-helices H and I (H-I loop), the AD, CBS1, and CBS2. In contrast, MTSET has no effect on channels in which cysteine residues are engineered into intracellular regions that are dispensable for regulation. These studies together with our previous work suggest that binding and unbinding of the AD to the Bateman domain dimer induces conformational changes that are transduced to channel membrane domains via the H-I loop. Our findings provide new, to our knowledge, insights into the roles of CLC Bateman domains and the structurefunction relationships that govern the regulation of CLC protein activity by diverse ligands and signaling pathways.

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Magnesium depletion extends fission yeast lifespan via general amino acid control activation

et al. 2021

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Mg ²⁺ -sensing mechanism of Mg ²⁺ transporter MgtE probed by molecular dynamics study

Cited by 56 publications

References 29 publications

Cystathionine β-Synthase (CBS) Domains 1 and 2 Fulfill Different Roles in Ionic Strength Sensing of the ATP-binding Cassette (ABC) Transporter OpuA

Cystathionine β-Synthase (CBS) Domains 1 and 2 Fulfill Different Roles in Ionic Strength Sensing of the ATP-binding Cassette (ABC) Transporter OpuA

Role of CBS and Bateman Domains in Phosphorylation-Dependent Regulation of a CLC Anion Channel

Magnesium depletion extends fission yeast lifespan via general amino acid control activation

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Mg 2+ -sensing mechanism of Mg 2+ transporter MgtE probed by molecular dynamics study

Cited by 56 publications

References 29 publications

Cystathionine β-Synthase (CBS) Domains 1 and 2 Fulfill Different Roles in Ionic Strength Sensing of the ATP-binding Cassette (ABC) Transporter OpuA

Cystathionine β-Synthase (CBS) Domains 1 and 2 Fulfill Different Roles in Ionic Strength Sensing of the ATP-binding Cassette (ABC) Transporter OpuA

Role of CBS and Bateman Domains in Phosphorylation-Dependent Regulation of a CLC Anion Channel

Magnesium depletion extends fission yeast lifespan via general amino acid control activation

Contact Info

Product

Resources

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Mg ²⁺ -sensing mechanism of Mg ²⁺ transporter MgtE probed by molecular dynamics study