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Plant cytoplasmic GAPDH: redox post-translational modifications and moonlighting properties.

Zaffagnini M, Fermani S, Costa A, Lemaire SD, Trost P - Front Plant Sci (2013)

Bottom Line: A general feature of all GAPDH proteins is the presence of an acidic catalytic cysteine in the active site that is overly sensitive to oxidative modifications, including glutathionylation and S-nitrosylation.Oxidative modifications inhibit GAPDH activity, but might enable additional functions in plant cells.The aim of this review is to detail the molecular mechanisms underlying the redox regulation of plant cytoplasmic GAPDH in the light of its crystal structure, and to provide a brief inventory of the well known redox-dependent multi-facetted properties of animal GAPDH, together with the emerging roles of oxidatively modified GAPDH in stress signaling pathways in plants.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Plant Redox Biology, Department of Pharmacy and Biotechnology, University of Bologna Bologna, Italy.

ABSTRACT
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a ubiquitous enzyme involved in glycolysis and shown, particularly in animal cells, to play additional roles in several unrelated non-metabolic processes such as control of gene expression and apoptosis. This functional versatility is regulated, in part at least, by redox post-translational modifications that alter GAPDH catalytic activity and influence the subcellular localization of the enzyme. In spite of the well established moonlighting (multifunctional) properties of animal GAPDH, little is known about non-metabolic roles of GAPDH in plants. Plant cells contain several GAPDH isoforms with different catalytic and regulatory properties, located both in the cytoplasm and in plastids, and participating in glycolysis and the Calvin-Benson cycle. A general feature of all GAPDH proteins is the presence of an acidic catalytic cysteine in the active site that is overly sensitive to oxidative modifications, including glutathionylation and S-nitrosylation. In Arabidopsis, oxidatively modified cytoplasmic GAPDH has been successfully used as a tool to investigate the role of reduced glutathione, thioredoxins and glutaredoxins in the control of different types of redox post-translational modifications. Oxidative modifications inhibit GAPDH activity, but might enable additional functions in plant cells. Mounting evidence support the concept that plant cytoplasmic GAPDH may fulfill alternative, non-metabolic functions that are triggered by redox post-translational modifications of the protein under stress conditions. The aim of this review is to detail the molecular mechanisms underlying the redox regulation of plant cytoplasmic GAPDH in the light of its crystal structure, and to provide a brief inventory of the well known redox-dependent multi-facetted properties of animal GAPDH, together with the emerging roles of oxidatively modified GAPDH in stress signaling pathways in plants.

No MeSH data available.


Related in: MedlinePlus

Partial sequence alignment of GAPDH isoforms from different organisms. The alignment is focused on two highly conserved regions of GAPDH, one belonging to the coenzyme-binding domain and one belonging to the catalytic domain. The first (N-terminal) region includes the strictly conserved sequence NGFGRIGR and other important residues for the binding of the pyridine nucleotide cofactor (Asp-35, Phe-37). The second region, located in the central part of GAPDH sequences, contains several residues involved in substrate binding including the catalytic cysteine (Cys-154), but also a second cysteine close to the active site (Cys-158) and His-181, essential for activating Cys-154. Residues are numbered according to the sequence of Oryza sativa (Os) cytoplasmic GAPDH (GAPC). Abbreviation and accession numbers: OsGAPC, Oryza sativa GAPC, Q0J8A4.1; AtGAPC1, Arabidopsis thaliana GAPC1, AEE74039.1; AtGAPC2, Arabidopsis thaliana GAPC1, AEE29016.1; AtGAPCp1, Arabidopsis thaliana GAPCp1, Q9SAJ6.1; AtGAPCp2, Arabidopsis thaliana GAPCp2, Q5E924.1; AtGAPA, Arabidopsis thaliana GAPA, AEE77191.1; AtGAPB, Arabidopsis thaliana GAPB; HsGAPDH, Homo sapiens GAPDH, P04406.3; BsGAPDH, Bacillus stearothermophilus GAPDH, PDB code 2DBV; HaGAPDH, Homarus americanus GAPDH, P00357; EcGAPDH, Escherichia coli GAPDH, ACI83895.1. Invariant residues are on a blue background while yellow background indicated residues with strongly similar properties. Catalytic Cys-154 (corresponding to Cys-149 and Cys-156 in BsGAPDH and AtGAPCs, respectively) and His-181 (corresponding to His-176 and His-183 in BsGAPDH and AtGAPCs, respectively) are highlighted by arrows. The sequences were aligned with the Clustal Omega program ().
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Figure 2: Partial sequence alignment of GAPDH isoforms from different organisms. The alignment is focused on two highly conserved regions of GAPDH, one belonging to the coenzyme-binding domain and one belonging to the catalytic domain. The first (N-terminal) region includes the strictly conserved sequence NGFGRIGR and other important residues for the binding of the pyridine nucleotide cofactor (Asp-35, Phe-37). The second region, located in the central part of GAPDH sequences, contains several residues involved in substrate binding including the catalytic cysteine (Cys-154), but also a second cysteine close to the active site (Cys-158) and His-181, essential for activating Cys-154. Residues are numbered according to the sequence of Oryza sativa (Os) cytoplasmic GAPDH (GAPC). Abbreviation and accession numbers: OsGAPC, Oryza sativa GAPC, Q0J8A4.1; AtGAPC1, Arabidopsis thaliana GAPC1, AEE74039.1; AtGAPC2, Arabidopsis thaliana GAPC1, AEE29016.1; AtGAPCp1, Arabidopsis thaliana GAPCp1, Q9SAJ6.1; AtGAPCp2, Arabidopsis thaliana GAPCp2, Q5E924.1; AtGAPA, Arabidopsis thaliana GAPA, AEE77191.1; AtGAPB, Arabidopsis thaliana GAPB; HsGAPDH, Homo sapiens GAPDH, P04406.3; BsGAPDH, Bacillus stearothermophilus GAPDH, PDB code 2DBV; HaGAPDH, Homarus americanus GAPDH, P00357; EcGAPDH, Escherichia coli GAPDH, ACI83895.1. Invariant residues are on a blue background while yellow background indicated residues with strongly similar properties. Catalytic Cys-154 (corresponding to Cys-149 and Cys-156 in BsGAPDH and AtGAPCs, respectively) and His-181 (corresponding to His-176 and His-183 in BsGAPDH and AtGAPCs, respectively) are highlighted by arrows. The sequences were aligned with the Clustal Omega program ().

Mentions: A NAD+ molecule is bound to each enzyme subunit and anchored by several hydrogen bonds, either directly or through water molecules (Tien et al., 2012). In particular, the backbone atoms of the highly conserved N-terminal segment (Asn-9 to Arg-16: NGFGRIGR; Figure 2) interacts with the pyrophosphate moiety of the coenzyme, and the carboxyl group of Asp-35 (another strictly conserved residue of glycolytic GAPDHs, Figure 2) makes two hydrogen bonds with two adjacent hydroxyl groups (in position 2′ and 3′) of the ribose molecule linked to the adenine of NAD+. Other residues from the same subunit, and Asp-191 from the catalytic domain of the adjacent subunit further contribute to stabilize the cofactor. The correct holding of the adenine moiety of bound NAD+ is also determined by the conformation of Phe-37 side chain (conserved in glycolytic GAPDHs from higher plants and animals, but not in prokaryotes, Figure 2), that is 90°-rotated in apo-OsGAPC to allow the access of NAD+ to the coenzyme binding site (Tien et al., 2012).


Plant cytoplasmic GAPDH: redox post-translational modifications and moonlighting properties.

Zaffagnini M, Fermani S, Costa A, Lemaire SD, Trost P - Front Plant Sci (2013)

Partial sequence alignment of GAPDH isoforms from different organisms. The alignment is focused on two highly conserved regions of GAPDH, one belonging to the coenzyme-binding domain and one belonging to the catalytic domain. The first (N-terminal) region includes the strictly conserved sequence NGFGRIGR and other important residues for the binding of the pyridine nucleotide cofactor (Asp-35, Phe-37). The second region, located in the central part of GAPDH sequences, contains several residues involved in substrate binding including the catalytic cysteine (Cys-154), but also a second cysteine close to the active site (Cys-158) and His-181, essential for activating Cys-154. Residues are numbered according to the sequence of Oryza sativa (Os) cytoplasmic GAPDH (GAPC). Abbreviation and accession numbers: OsGAPC, Oryza sativa GAPC, Q0J8A4.1; AtGAPC1, Arabidopsis thaliana GAPC1, AEE74039.1; AtGAPC2, Arabidopsis thaliana GAPC1, AEE29016.1; AtGAPCp1, Arabidopsis thaliana GAPCp1, Q9SAJ6.1; AtGAPCp2, Arabidopsis thaliana GAPCp2, Q5E924.1; AtGAPA, Arabidopsis thaliana GAPA, AEE77191.1; AtGAPB, Arabidopsis thaliana GAPB; HsGAPDH, Homo sapiens GAPDH, P04406.3; BsGAPDH, Bacillus stearothermophilus GAPDH, PDB code 2DBV; HaGAPDH, Homarus americanus GAPDH, P00357; EcGAPDH, Escherichia coli GAPDH, ACI83895.1. Invariant residues are on a blue background while yellow background indicated residues with strongly similar properties. Catalytic Cys-154 (corresponding to Cys-149 and Cys-156 in BsGAPDH and AtGAPCs, respectively) and His-181 (corresponding to His-176 and His-183 in BsGAPDH and AtGAPCs, respectively) are highlighted by arrows. The sequences were aligned with the Clustal Omega program ().
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3824636&req=5

Figure 2: Partial sequence alignment of GAPDH isoforms from different organisms. The alignment is focused on two highly conserved regions of GAPDH, one belonging to the coenzyme-binding domain and one belonging to the catalytic domain. The first (N-terminal) region includes the strictly conserved sequence NGFGRIGR and other important residues for the binding of the pyridine nucleotide cofactor (Asp-35, Phe-37). The second region, located in the central part of GAPDH sequences, contains several residues involved in substrate binding including the catalytic cysteine (Cys-154), but also a second cysteine close to the active site (Cys-158) and His-181, essential for activating Cys-154. Residues are numbered according to the sequence of Oryza sativa (Os) cytoplasmic GAPDH (GAPC). Abbreviation and accession numbers: OsGAPC, Oryza sativa GAPC, Q0J8A4.1; AtGAPC1, Arabidopsis thaliana GAPC1, AEE74039.1; AtGAPC2, Arabidopsis thaliana GAPC1, AEE29016.1; AtGAPCp1, Arabidopsis thaliana GAPCp1, Q9SAJ6.1; AtGAPCp2, Arabidopsis thaliana GAPCp2, Q5E924.1; AtGAPA, Arabidopsis thaliana GAPA, AEE77191.1; AtGAPB, Arabidopsis thaliana GAPB; HsGAPDH, Homo sapiens GAPDH, P04406.3; BsGAPDH, Bacillus stearothermophilus GAPDH, PDB code 2DBV; HaGAPDH, Homarus americanus GAPDH, P00357; EcGAPDH, Escherichia coli GAPDH, ACI83895.1. Invariant residues are on a blue background while yellow background indicated residues with strongly similar properties. Catalytic Cys-154 (corresponding to Cys-149 and Cys-156 in BsGAPDH and AtGAPCs, respectively) and His-181 (corresponding to His-176 and His-183 in BsGAPDH and AtGAPCs, respectively) are highlighted by arrows. The sequences were aligned with the Clustal Omega program ().
Mentions: A NAD+ molecule is bound to each enzyme subunit and anchored by several hydrogen bonds, either directly or through water molecules (Tien et al., 2012). In particular, the backbone atoms of the highly conserved N-terminal segment (Asn-9 to Arg-16: NGFGRIGR; Figure 2) interacts with the pyrophosphate moiety of the coenzyme, and the carboxyl group of Asp-35 (another strictly conserved residue of glycolytic GAPDHs, Figure 2) makes two hydrogen bonds with two adjacent hydroxyl groups (in position 2′ and 3′) of the ribose molecule linked to the adenine of NAD+. Other residues from the same subunit, and Asp-191 from the catalytic domain of the adjacent subunit further contribute to stabilize the cofactor. The correct holding of the adenine moiety of bound NAD+ is also determined by the conformation of Phe-37 side chain (conserved in glycolytic GAPDHs from higher plants and animals, but not in prokaryotes, Figure 2), that is 90°-rotated in apo-OsGAPC to allow the access of NAD+ to the coenzyme binding site (Tien et al., 2012).

Bottom Line: A general feature of all GAPDH proteins is the presence of an acidic catalytic cysteine in the active site that is overly sensitive to oxidative modifications, including glutathionylation and S-nitrosylation.Oxidative modifications inhibit GAPDH activity, but might enable additional functions in plant cells.The aim of this review is to detail the molecular mechanisms underlying the redox regulation of plant cytoplasmic GAPDH in the light of its crystal structure, and to provide a brief inventory of the well known redox-dependent multi-facetted properties of animal GAPDH, together with the emerging roles of oxidatively modified GAPDH in stress signaling pathways in plants.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Plant Redox Biology, Department of Pharmacy and Biotechnology, University of Bologna Bologna, Italy.

ABSTRACT
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a ubiquitous enzyme involved in glycolysis and shown, particularly in animal cells, to play additional roles in several unrelated non-metabolic processes such as control of gene expression and apoptosis. This functional versatility is regulated, in part at least, by redox post-translational modifications that alter GAPDH catalytic activity and influence the subcellular localization of the enzyme. In spite of the well established moonlighting (multifunctional) properties of animal GAPDH, little is known about non-metabolic roles of GAPDH in plants. Plant cells contain several GAPDH isoforms with different catalytic and regulatory properties, located both in the cytoplasm and in plastids, and participating in glycolysis and the Calvin-Benson cycle. A general feature of all GAPDH proteins is the presence of an acidic catalytic cysteine in the active site that is overly sensitive to oxidative modifications, including glutathionylation and S-nitrosylation. In Arabidopsis, oxidatively modified cytoplasmic GAPDH has been successfully used as a tool to investigate the role of reduced glutathione, thioredoxins and glutaredoxins in the control of different types of redox post-translational modifications. Oxidative modifications inhibit GAPDH activity, but might enable additional functions in plant cells. Mounting evidence support the concept that plant cytoplasmic GAPDH may fulfill alternative, non-metabolic functions that are triggered by redox post-translational modifications of the protein under stress conditions. The aim of this review is to detail the molecular mechanisms underlying the redox regulation of plant cytoplasmic GAPDH in the light of its crystal structure, and to provide a brief inventory of the well known redox-dependent multi-facetted properties of animal GAPDH, together with the emerging roles of oxidatively modified GAPDH in stress signaling pathways in plants.

No MeSH data available.


Related in: MedlinePlus