Crystal Structures of the CBS and DRTGG Domains of the Regulatory Region of Clostridium perfringens Pyrophosphatase Complexed with the Inhibitor, AMP, and Activator, Diadenosine Tetraphosphate

Tuominen, Heidi; Salminen, Anu; Oksanen, Esko; Jamsen, J.A.; Heikkilä, Outi; Lehtiö, L.; Magretova, Natalia N.; Goldman, Adrian; Baykov, Alexander A.; Lahti, Reijo

doi:10.1016/j.jmb.2010.03.019

Cited by 41 publications

(86 citation statements)

References 63 publications

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“…The ability of CBSX1 ( Figure 3C) and CBSX2 (see Supplemental Figure 5C online) to increase the activity of all four Trxs was augmented by AMP binding, but ADP and ATP did not show this enhancing effect (see Supplemental Figure 5B online). Our structural analysis revealed that several basic residues from each subunit, namely, Lys-201, Arg-203, Arg-204, and Arg-220, form a ligand binding pocket ( Figure 2C, right), and previous studies have demonstrated the presence of adenosine-containing ligands in similar pockets in the structures of several CBS domain proteins (Xiao et al, 2007;King et al, 2008;Tuominen et al, 2010). As noted, CBSX2 is an antiparallel dimer and thus most likely accommodates two adenosine-containing ligands simultaneously in one pocket (Figure 2C).…”

Section: Cbsx1 Activates All Four Trxs In the Chloroplast And Furthersupporting

confidence: 74%

“…It is also characterized by a unique ;1208 bend at the side of the molecule ( Figure 2B). This feature contrasts with all other parallel and antiparallel CBS domain proteins, which are characterized by an ;1808 flat structure at the side (Ragunathan et al, 2008;Tuominen et al, 2010). The orientation and molecular symmetry of CBSX2 may determine the interacting surface for its ligands, which affect its function.…”

Section: Structural Features Of Cbsx Proteinsmentioning

confidence: 92%

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Single Cystathionine β-Synthase Domain–Containing Proteins Modulate Development by Regulating the Thioredoxin System in Arabidopsis

Yoo

Jeong

et al. 2011

The Plant Cell

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Plant thioredoxins (Trxs) participate in two redox systems found in different cellular compartments: the NADP-Trx system (NTS) in the cytosol and mitochondria and the ferredoxin-Trx system (FTS) in the chloroplast, where they function as redox regulators by regulating the activity of various target enzymes. The identities of the master regulators that maintain cellular homeostasis and modulate timed development through redox regulating systems have remained completely unknown. Here, we show that proteins consisting of a single cystathionine b-synthase (CBS) domain pair stabilize cellular redox homeostasis and modulate plant development via regulation of Trx systems by sensing changes in adenosine-containing ligands. We identified two CBS domain-containing proteins in Arabidopsis thaliana, CBSX1 and CBSX2, which are localized to the chloroplast, where they activate all four Trxs in the FTS. CBSX3 was found to regulate mitochondrial Trx members in the NTS. CBSX1 directly regulates Trxs and thereby controls H 2 O 2 levels and regulates lignin polymerization in the anther endothecium. It also affects plant growth by regulating Calvin cycle enzymes, such as malate dehydrogenase, via homeostatic regulation of Trxs. Based on our findings, we suggest that the CBSX proteins (or a CBS pair) are ubiquitous redox regulators that regulate Trxs in the FTS and NTS to modulate development and maintain homeostasis under conditions that are threatening to the cell.

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Section: Cbsx1 Activates All Four Trxs In the Chloroplast And Furthersupporting

confidence: 74%

Section: Structural Features Of Cbsx Proteinsmentioning

confidence: 92%

Single Cystathionine β-Synthase Domain–Containing Proteins Modulate Development by Regulating the Thioredoxin System in Arabidopsis

Yoo

Jeong

et al. 2011

The Plant Cell

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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%

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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“…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%

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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Crystal Structures of the CBS and DRTGG Domains of the Regulatory Region of Clostridium perfringens Pyrophosphatase Complexed with the Inhibitor, AMP, and Activator, Diadenosine Tetraphosphate

Cited by 41 publications

References 63 publications

Single Cystathionine β-Synthase Domain–Containing Proteins Modulate Development by Regulating the Thioredoxin System in Arabidopsis

Single Cystathionine β-Synthase Domain–Containing Proteins Modulate Development by Regulating the Thioredoxin System in Arabidopsis

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

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

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