Molecular Phylogenetics of a Protein Repair Methyltransferase

Kagan, Ron M.; McFadden, Helen J; McFadden, Philip N.; O’Connor, Clare M.; Clarke, Steven

doi:10.1016/s0305-0491(96)00333-1

Cited by 48 publications

(47 citation statements)

References 32 publications

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“…3B). The analysis supports the ubiquitous distribution of PIMTs with higher divergence among bacteria than eukaryotes, as suggested previously (Kagan et al, 1997;O'Connor, 2006). Among eukaryotes, plant PIMT proteins clustered together in one subgroup and are distinct from other subgroups of eukaryotes.…”

Section: Accelerated Aging Affects Pimt Activity and Enhances Isoasp supporting

confidence: 64%

“…Both CaPIMT2 and CaPIMT29 polypeptide sequences contain five conserved domains (preregion I, TISAPHMHA; region I, ALDVGSGTG/ALDVGS-G, where boldface text signifies the presence of these two amino acids in CaPIMT2 and absence in the splice variant CaPIMT29; region II, APYDAIHV; region III, QLKPGGRMVI; and postregion III, VRYPLTS [Kagan et al, 1997]), like other PIMT proteins; however, the CaPIMT29 isoform lacks two important amino acids (Gly and Thr) in region I (ALDVGS-G) due to the absence of 6 bp in its coding region. Interestingly, region I (ALDVGSGTG) is important for the catalytic activity of enzymes utilizing AdoMet, where Gly is one of the key active-site amino acids (Smith et al, 2002).…”

Section: Accelerated Aging Affects Pimt Activity and Enhances Isoasp mentioning

confidence: 99%

“…PIMT has been considered as an ancient and highly conserved enzyme that is widely distributed in evolutionarily diverged organisms such as eubacteria, archaebacteria, protozoa, fungi, nematodes, mammals, and plants (Kagan et al, 1997;O'Connor, 2006).…”

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PROTEIN l-ISOASPARTYL METHYLTRANSFERASE2 Is Differentially Expressed in Chickpea and Enhances Seed Vigor and Longevity by Reducing Abnormal Isoaspartyl Accumulation Predominantly in Seed Nuclear Proteins

et al. 2013

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PROTEIN L-ISOASPARTYL METHYLTRANSFERASE (PIMT) is a widely distributed protein-repairing enzyme that catalyzes the conversion of abnormal L-isoaspartyl residues in spontaneously damaged proteins to normal aspartyl residues. This enzyme is encoded by two divergent genes (PIMT1 and PIMT2) in plants, unlike many other organisms. While the biological role of PIMT1 has been elucidated, the role and significance of the PIMT2 gene in plants is not well defined. Here, we isolated the PIMT2 gene (CaPIMT2) from chickpea (Cicer arietinum), which exhibits a significant increase in isoaspartyl residues in seed proteins coupled with reduced germination vigor under artificial aging conditions. The CaPIMT2 gene is found to be highly divergent and encodes two possible isoforms (CaPIMT2 and CaPIMT29) differing by two amino acids in the region I catalytic domain through alternative splicing. Unlike CaPIMT1, both isoforms possess a unique 56-amino acid amino terminus and exhibit similar yet distinct enzymatic properties. Expression analysis revealed that CaPIMT2 is differentially regulated by stresses and abscisic acid. Confocal visualization of stably expressed green fluorescent protein-fused PIMT proteins and cell fractionation-immunoblot analysis revealed that apart from the plasma membrane, both CaPIMT2 isoforms localize predominantly in the nucleus, while CaPIMT1 localizes in the cytosol. Remarkably, CaPIMT2 enhances seed vigor and longevity by repairing abnormal isoaspartyl residues predominantly in nuclear proteins upon seed-specific expression in Arabidopsis (Arabidopsis thaliana), while CaPIMT1 enhances seed vigor and longevity by repairing such abnormal proteins mainly in the cytosolic fraction. Together, our data suggest that CaPIMT2 has most likely evolved through gene duplication, followed by subfunctionalization to specialize in repairing the nuclear proteome.

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Section: Accelerated Aging Affects Pimt Activity and Enhances Isoasp supporting

confidence: 64%

Section: Accelerated Aging Affects Pimt Activity and Enhances Isoasp mentioning

confidence: 99%

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PROTEIN l-ISOASPARTYL METHYLTRANSFERASE2 Is Differentially Expressed in Chickpea and Enhances Seed Vigor and Longevity by Reducing Abnormal Isoaspartyl Accumulation Predominantly in Seed Nuclear Proteins

et al. 2013

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“…PIMT is a highly conserved enzyme that has been described in a wide range of organisms, including gram-negative bacteria, plants, invertebrates, such as nematodes, and vertebrates, including humans (Kagan et al, 1997b). Furthermore, in Escherichia coli, Caenorhabditis elegans, Drosophila melanogaster, and mice (Reissner and Aswad, 2003;Shimizu et al, 2005), there is genetic evidence that PIMT plays a protective role in vivo to overcome environmental stress in aging tissues.…”

Section: Introductionmentioning

confidence: 99%

Protein Repairl-Isoaspartyl Methyltransferase1 Is Involved in Both Seed Longevity and Germination Vigor inArabidopsis

et al. 2008

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The formation of abnormal amino acid residues is a major source of spontaneous age-related protein damage in cells. The protein L-isoaspartyl methyltransferase (PIMT) combats protein misfolding resulting from L-isoaspartyl formation by catalyzing the conversion of abnormal L-isoaspartyl residues to their normal L-aspartyl forms. In this way, the PIMT repair enzyme system contributes to longevity and survival in bacterial and animal kingdoms. Despite the discovery of PIMT activity in plants two decades ago, the role of this enzyme during plant stress adaptation and in seed longevity remains undefined. In this work, we have isolated Arabidopsis thaliana lines exhibiting altered expression of PIMT1, one of the two genes encoding the PIMT enzyme in Arabidopsis. PIMT1 overaccumulation reduced the accumulation of L-isoaspartyl residues in seed proteins and increased both seed longevity and germination vigor. Conversely, reduced PIMT1 accumulation was associated with an increase in the accumulation of L-isoaspartyl residues in the proteome of freshly harvested dry mature seeds, thus leading to heightened sensitivity to aging treatments and loss of seed vigor under stressful germination conditions. These data implicate PIMT1 as a major endogenous factor that limits abnormal L-isoaspartyl accumulation in seed proteins, thereby improving seed traits such as longevity and vigor. The PIMT repair pathway likely works in concert with other anti-aging pathways to actively eliminate deleterious protein products, thus enabling successful seedling establishment and strengthening plant proliferation in natural environments.

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“…This methyltransferase is found in a wide array of organisms including eubacteria (10), plants (11,12), nematodes (13), insects (14), and mammals (15). Its amino acid sequence is highly conserved (16). Its functional importance to the bacterium Escherichia coli, the nematode worm Caenorhabditis elegans, and mice has been assessed by analyzing the effect of knockout mutations of its structural genes.…”

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Protein Repair Methyltransferase from the Hyperthermophilic Archaeon Pyrococcus furiosus

Thapar

Griffith

Yeates

et al. 2002

Journal of Biological Chemistry

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Protein L-isoaspartate-(D-aspartate)O-methyltransferases (EC 2.1.1.77), present in a wide variety of prokaryotic and eukaryotic organisms, can initiate the conversion of abnormal L-isoaspartyl residues that arise spontaneously with age to normal L-aspartyl residues. In addition, the mammalian enzyme can recognize spontaneously racemized D-aspartyl residues for conversion to L-aspartyl residues, although no such activity has been seen to date for enzymes from lower animals or prokaryotes. In this work, we characterize the enzyme from the hyperthermophilic archaebacterium Pyrococcus furiosus. Remarkably, this methyltransferase catalyzes both L-isoaspartyl and D-aspartyl methylation reactions in synthetic peptides with affinities that can be significantly higher than those of the human enzyme, previously the most catalytically efficient species known. Analysis of the common features of L-isoaspartyl and D-aspartyl residues suggested that the basic substrate recognition element for this enzyme may be mimicked by an N-terminal succinyl peptide. We tested this hypothesis with a number of synthetic peptides using both the P. furiosus and the human enzyme. We found that peptides devoid of aspartyl residues but containing the N-succinyl group were in fact methyl esterified by both enzymes. The recent structure determined for the Lisoaspartyl methyltransferase from P. furiosus complexed with an L-isoaspartyl peptide supports this mode of methyl-acceptor recognition. The combination of the thermophilicity and the high affinity binding of methylaccepting substrates makes the P. furiosus enzyme useful both as a reagent for detecting isomerized and racemized residues in damaged proteins and for possible human therapeutic use in repairing damaged proteins in extracellular environments where the cytosolic enzyme is not normally found.) is a repair enzyme that catalyzes the S-adenosylmethionine (AdoMet)-dependent 1 methyl esterification of the ␣-carboxyl group of L-isoaspartyl residues that originate from the spontaneous degradation of aspartic acid and asparagine residues in proteins (1-5). The enzyme-mediated methylation reaction is followed by nonenzymatic steps that result in the net conversion of L-isoaspartyl residues to L-aspartyl residues, representing a potentially important mechanism for avoiding the accumulation of damaged proteins as cells age (4 -9). This methyltransferase is found in a wide array of organisms including eubacteria (10), plants (11, 12), nematodes (13), insects (14), and mammals (15). Its amino acid sequence is highly conserved (16). Its functional importance to the bacterium Escherichia coli, the nematode worm Caenorhabditis elegans, and mice has been assessed by analyzing the effect of knockout mutations of its structural genes. In E. coli, methyltransferasedeficient cells are more sensitive to stress in the stationary phase (17), whereas knockout worms show poorer survival in the dauer phase (18). Methyltransferase-deficient mice suffer fatal seizures at an early age (19 -21). Interestingly, the e...

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Molecular Phylogenetics of a Protein Repair Methyltransferase

Cited by 48 publications

References 32 publications

PROTEIN l-ISOASPARTYL METHYLTRANSFERASE2 Is Differentially Expressed in Chickpea and Enhances Seed Vigor and Longevity by Reducing Abnormal Isoaspartyl Accumulation Predominantly in Seed Nuclear Proteins

PROTEIN l-ISOASPARTYL METHYLTRANSFERASE2 Is Differentially Expressed in Chickpea and Enhances Seed Vigor and Longevity by Reducing Abnormal Isoaspartyl Accumulation Predominantly in Seed Nuclear Proteins

Protein Repairl-Isoaspartyl Methyltransferase1 Is Involved in Both Seed Longevity and Germination Vigor inArabidopsis

Protein Repair Methyltransferase from the Hyperthermophilic Archaeon Pyrococcus furiosus

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