RESUMO
Neurological diseases are characterized by the complexity of care and by a constant and changing disability. More and more frequently, their impact on the clinical pathway remains unknown. Seven postgraduate rehabilitation students (Master coordination du handicap, université Pierre-et-Marie-Curie, Paris) reconstructed the clinical pathway of 123 patients with various neurological diseases: multiple sclerosis, Alzheimer disease, amyotrophic lateral sclerosis, spinal trauma, Parkinson disease and brain tumors. There was a significant correlation between disease duration and the number of specialists involved in care, the number of prescribed drugs and the number of short-term hospitalizations; there was no correlation with age. This result suggests that with time an increasing number of complications related to the initial neurological disease developed. Hospitalization in rehabilitation units was highly correlated with the degree of disability and also with the help received by the patients during the course of their disease. This result suggests that these hospitalizations were a direct consequence of burn out among relatives. General practitioners (GP) were highly involved only during the initial part of the pathway, and their involvement rapidly declined thereafter, suggesting a probable relation with the specificities and the complexity of care for neurological diseases which induces a progressive transfer of responsibilities from the GP to the hospital. Social care was always incomplete and occurred too late during the course of the disease. The feeling by the patients that their care pathway was chaotic was highly correlated with the quality of the information given to the patient at the time of the announcement of their disease. This study confirms that cares for neurological diseases is highly specific and that expert centers and coordination networks are in a key position to ensure an efficient care pathway.
Assuntos
Procedimentos Clínicos/organização & administração , Pessoas com Deficiência , Doenças Neurodegenerativas/terapia , Pessoal Técnico de Saúde/estatística & dados numéricos , Progressão da Doença , Hospitalização/estatística & dados numéricos , Humanos , Doenças Neurodegenerativas/epidemiologia , Doenças Neurodegenerativas/psicologia , Prática Profissional/estatística & dados numéricos , Qualidade de Vida , Meio SocialRESUMO
BACKGROUND: Acute liver failure (ALF) models in pigs have been widely used for evaluating newly developed liver support systems. But hardly any guidelines are available for the surgical methods and the clinical management. METHODS: The study validated several standard operating procedures describing in detail the surgical method and intensive care monitoring and treatment (control of potassium, glucose and bicarbonate levels, cardiovascular and intracranial pressure monitoring, etc.). ALF was induced in animals with a mean of 56 kg. Two surgical methods were compared: ligation of hepatic arteries with either end-to-side portacaval shunt (ESPS) and bile duct ligation or side-to-side portacaval shunt (SSPS) without bile duct ligation. RESULTS: During total portal vein clamping, the animals in the ESPS group developed severe hypotension, splanchnic congestion and metabolic acidosis. One animal died after approximately 1.5 h. This model therefore represents a multiorgan failure model rather than an isolated ALF model. In the SSPS group, none of these side effects were observed, while clinical, laboratory and histopathological signs of ALF were evident. CONCLUSIONS: A reproducible model in pigs representing ALF can be established with the help of the standardized monitoring and treatment procedures presented.
Assuntos
Isquemia/etiologia , Isquemia/terapia , Falência Hepática Aguda/etiologia , Falência Hepática Aguda/terapia , Fígado/irrigação sanguínea , Animais , Ductos Biliares/cirurgia , Modelos Animais de Doenças , Feminino , Veias Hepáticas/cirurgia , Humanos , Isquemia/fisiopatologia , Ligadura , Fígado/fisiopatologia , Fígado/cirurgia , Falência Hepática Aguda/fisiopatologia , Testes de Função Hepática , Monitorização Fisiológica , Derivação Portocava Cirúrgica , Veia Porta/cirurgia , Sus scrofaRESUMO
Aminoacyl tRNA synthetases--enzymes that catalyze the first step of protein synthesis--in mammalian cells are now known to have expanded functions, including activities in signal transduction pathways, such as those for angiogenesis and inflammation. The native synthetases themselves are procytokines, having no signal transduction activities. After alternative splicing or natural proteolysis, specific fragments that are potent cytokines and that interact with specific receptors on cell surfaces are released. In this manner, a natural fragment of human tyrosyl tRNA synthetase (TyrRS), mini-TyrRS, has been shown to act as a proangiogenic cytokine. The mechanistic basis for the action of mini-TyrRS in angiogenesis has yet to be established. Here, we show that mini-TyrRS is exported from endothelial cells when they are treated with tumor necrosis factor-alpha. Mini-TyrRS binds to vascular endothelial cells and activates an array of angiogenic signal transduction pathways. Mini-TyrRS-induced angiogenesis requires the activation of vascular endothelial growth factor receptor-2 (VEGFR2/Flk-1/KDR). Mini-TyrRS stimulates VEGFR2 phosphorylation in a VEGF-independent manner, suggesting VEGFR2 transactivation. Transactivation of VEGFR2 and downstream angiogenesis require an intact Glu-Leu-Arg (ELR) motif in mini-TyrRS, which is important for its cytokine activity. These studies therefore suggest a mechanism by which mini-TyrRS induces angiogenesis in endothelial cells and provide further insight into the role of mini-TyrRS as a link between translation and angiogenesis.
Assuntos
Endotélio Vascular/fisiologia , Fragmentos de Peptídeos/metabolismo , Tirosina-tRNA Ligase/metabolismo , Animais , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Microscopia de Fluorescência , Neovascularização Fisiológica/efeitos dos fármacos , Permeabilidade/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/fisiologiaRESUMO
Editing reactions are essential for the high fidelity of information transfer in processes such as replication, RNA splicing, and protein synthesis. The accuracy of interpretation of the genetic code is enhanced by the editing reactions of aminoacyl transfer RNA (tRNA) synthetases, whereby amino acids are prevented from being attached to the wrong tRNAs. Amino acid discrimination is achieved through sieves that may overlap with or coincide with the amino acid binding site. With the class I Escherichia coli isoleucine tRNA synthetase, which activates isoleucine and occasionally misactivates valine, as an example, a rationally chosen mutant enzyme was constructed that lacks entirely its normal strong ability to distinguish valine from isoleucine by the initial amino acid recognition sieve. The misactivated valine, however, is still eliminated by hydrolytic editing reactions. These data suggest that there is a distinct sieve for editing that is functionally independent of the amino acid binding site.
Assuntos
Isoleucina-tRNA Ligase/metabolismo , Isoleucina/metabolismo , Edição de RNA , Valina/metabolismo , Trifosfato de Adenosina/metabolismo , Sítios de Ligação , Escherichia coli/enzimologia , Isoleucina-tRNA Ligase/química , Isoleucina-tRNA Ligase/genética , Cinética , Mutação , Estrutura Secundária de Proteína , RNA de Transferência de Isoleucina/metabolismoRESUMO
The genetic code is based on specific interactions between transfer RNA (tRNA) synthetases and their cognate tRNAs. The anticodons for methionine and isoleucine tRNAs differ by a single nucleotide, and changing this nucleotide in an isoleucine tRNA is sufficient to change aminoacylation specificity to methionine. Results of combinatorial mutagenesis of an anticodon-binding-helix loop peptide were used to design a hybrid sequence composed of amino acid residues from methionyl- and isoleucyl-tRNA synthetases. When the hybrid sequence was transplanted into isoleucyl-tRNA synthetase, active enzyme was generated in vivo and in vitro. The transplanted peptide did not confer function to methionyl-tRNA synthetase, but the substitution of a single amino acid within the transplanted peptide conferred methionylation and prevented isoleucylation. Thus, the swap of a single amino acid in the transplanted peptide switches specificity between anticodons that differ by one nucleotide.
Assuntos
Anticódon , Isoleucina-tRNA Ligase/metabolismo , Metionina tRNA Ligase/metabolismo , RNA de Transferência de Isoleucina/metabolismo , RNA de Transferência de Metionina/metabolismo , Sequência de Aminoácidos , Teste de Complementação Genética , Sequências Hélice-Alça-Hélice , Isoleucina-tRNA Ligase/química , Isoleucina-tRNA Ligase/genética , Metionina tRNA Ligase/química , Metionina tRNA Ligase/genética , Dados de Sequência Molecular , Mutagênese , Oligopeptídeos/química , Oligopeptídeos/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Aminoacilação de RNA de TransferênciaRESUMO
Aminoacyl-tRNA synthetases catalyze aminoacylation of transfer RNAs (tRNAs). It is shown that human tyrosyl-tRNA synthetase can be split into two fragments with distinct cytokine activities. The endothelial monocyte-activating polypeptide II-like carboxy-terminal domain has potent leukocyte and monocyte chemotaxis activity and stimulates production of myeloperoxidase, tumor necrosis factor-alpha, and tissue factor. The catalytic amino-terminal domain binds to the interleukin-8 type A receptor and functions as an interleukin-8-like cytokine. Under apoptotic conditions in cell culture, the full-length enzyme is secreted, and the two cytokine activities can be generated by leukocyte elastase, an extracellular protease. Secretion of this tRNA synthetase may contribute to apoptosis both by arresting translation and producing needed cytokines.
Assuntos
Citocinas , Interleucina-8/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas de Ligação a RNA/metabolismo , Tirosina-tRNA Ligase/metabolismo , Sequência de Aminoácidos , Antígenos CD/metabolismo , Apoptose , Ligação Competitiva , Domínio Catalítico , Quimiotaxia de Leucócito , Humanos , Interleucina-8/farmacologia , Elastase de Leucócito/metabolismo , Dados de Sequência Molecular , Monócitos/fisiologia , Proteínas de Neoplasias/farmacologia , Neutrófilos/metabolismo , Neutrófilos/fisiologia , Proteínas de Ligação a RNA/farmacologia , Receptores de Interleucina/metabolismo , Receptores de Interleucina-8A , Proteínas Recombinantes/metabolismo , Transdução de Sinais , Células Tumorais Cultivadas , Tirosina-tRNA Ligase/química , Tirosina-tRNA Ligase/farmacologiaRESUMO
The three-dimensional structure of most enzymes is unknown; however, many enzymes may have structural motifs similar to those in the known structures of functionally related enzymes. Evidence is presented that an enzyme of unknown structure [Ile-transfer RNA (tRNA) synthetase] may share a functionally important structural motif with an enzyme of related function (Tyr-tRNA synthetase). This approach involves (i) identifying segments of Ile-tRNA synthetase that have been unusually conserved during evolution, (ii) predicting the function of one such segment by assuming a structural relation between Ile-tRNA synthetase and Tyr-tRNA synthetase, and (iii) testing the predicted function by mutagenesis and subsequent biochemical analysis. Random mutations were introduced by cassette mutagenesis into a ten-amino-acid segment of Ile-tRNA synthetase that was predicted to be involved in the formation of the binding site for isoleucine. Few amino acid substitutions appear to be tolerated in this region. However, one substitution (independently isolated twice) increased the Michaelis constant Km for isoleucine in the adenylate synthesis reaction by greater than 6000-fold, but had little effect on the Km for adenosine triphosphate, the apparent Km for tRNA, or the rate constant kcat.
Assuntos
Aminoacil-tRNA Sintetases , Isoleucina-tRNA Ligase , Sítios de Ligação , Análise Mutacional de DNA , Escherichia coli/enzimologia , Cinética , Conformação Proteica , Saccharomyces cerevisiae/enzimologia , Relação Estrutura-AtividadeRESUMO
Deletion of more than 400 amino acids from the carboxyl terminus of an enzyme causes a severe reduction in catalytic activity. Selected point mutations within the residual protein partially reverse the effects of the missing segment. The selection can yield mutants with activities at least ten times as high as those of the starting polypeptides. One well-characterized mutation, a single amino acid replacement in the residual polypeptide, increases the catalytic activity of the polypeptide by a factor of 5. The results suggest substantial potential for design of protein elements to compensate for missing polypeptide sequences. They also may reflect that progenitors of large aminoacyl-tRNA (transfer RNA) synthetases--one of which was used in these studies--were themselves much smaller.
Assuntos
Sequência de Aminoácidos , Enzimas/genética , Alanina-tRNA Ligase/genética , DNA Recombinante , Enzimas/metabolismo , Escherichia coli/enzimologia , Escherichia coli/genética , Engenharia Genética , Vetores Genéticos , Mutação , Ácidos Nucleicos Heteroduplexes/genética , PlasmídeosRESUMO
A seven-base pair microhelix that recapitulates a glycine transfer RNA (tRNA) acceptor helix can be specifically aminoacylated with glycine. A single base pair and the single-stranded discriminator base near the attachment site are essential for aminoacylation. These nucleotide sequence elements, and those in microhelices that can be charged with histidine and alanine, occur in the same positions and therefore overlap. Studies on a systematic set of sequence variants showed that no microhelix could be charged with more than one amino acid. Also, none of the three cognate aminoacyl-tRNA synthetases (aaRSs) gave a detectable amount of aminoacylation of the CCA trinucleotide that is common to the 3' ends of all tRNAs, showing that the specific acceptor stem nucleotide bases confer aminoacylation. An analysis of the relative contributions of these microhelices to overall tRNA recognition indicated that their interaction with aaRSs constitutes a substantial part of the recognition of the whole tRNAs.
Assuntos
Glicina-tRNA Ligase/metabolismo , RNA de Transferência de Glicina/química , Sequência de Bases , Ligação de Hidrogênio , Dados de Sequência Molecular , Conformação de Ácido Nucleico , RNA de Transferência de Glicina/metabolismo , RNA de Transferência de Glicina/ultraestrutura , Relação Estrutura-Atividade , Especificidade por Substrato , TermodinâmicaRESUMO
Many RNAs are complex, globular molecules formed from elements of secondary and tertiary structure analogous to those found in proteins. Little is known about recognition of RNAs by proteins. In the case of transfer RNAs (tRNAs), considerable evidence suggests that elements dispersed in both the one- and three-dimensional structure are important for recognition by aminoacyl tRNA synthetases. Fragments of alanine tRNA synthetase were created by in vitro manipulations of the cloned alaS gene and examined for their interaction with alanine-specific tRNA. Sequences essential for recognition were located near the middle of the polypeptide, juxtaposed to the carboxyl-terminal side of the domain for aminoacyl adenylate synthesis. The most essential part of the tRNA interaction strength and specificity was dependent on a sequence of fewer than 100 amino acids. Within this sequence, and in the context of the proper conformation, a segment of no more than 17 amino acids was responsible for 25% or more of the total synthetase-tRNA free energy of association. The results raise the possibility that an important part of specific RNA recognition by an aminoacyl tRNA synthetase involves a polypeptide segment that is short relative to the total size of the protein.
Assuntos
Aminoacil-tRNA Sintetases/metabolismo , RNA/metabolismo , Trifosfato de Adenosina/metabolismo , Alanina-tRNA Ligase/metabolismo , Sequência de Aminoácidos , Sequência de Bases , Clonagem Molecular , Escherichia coli/enzimologia , Aminoacil-RNA de Transferência/metabolismo , Relação Estrutura-Atividade , Especificidade por Substrato , TermodinâmicaRESUMO
Previous experimental results along with the structural modeling presented indicate that a nucleotide fold starts in the amino-terminal part of Escherichia coli isoleucyl-transfer RNA synthetase, a single chain polypeptide of 939 amino acids. Internal deletions were created in the region of the nucleotide fold. A set of deletions that collectively span 145 contiguous amino acids yielded active enzymes. Further extensions of the deletions yielded inactive or unstable proteins. The three-dimensional structure of an evidently homologous protein suggests that the active deletions lack portions of a segment that connects two parts of the nucleotide fold. Therefore, the results imply that removal of major sections of the polypeptide that connects these two parts of the fold does not result in major perturbation of the nucleotide binding site.
Assuntos
Aminoacil-tRNA Sintetases , Isoleucina-tRNA Ligase , Metionina tRNA Ligase , RNA de Transferência/metabolismo , Sequência de Aminoácidos , Proteínas de Bactérias , Sítios de Ligação , Escherichia coli/enzimologia , Ligação de Hidrogênio , Conformação Proteica , Relação Estrutura-Atividade , Aminoacilação de RNA de TransferênciaRESUMO
During translation errors of aminoacylation are corrected in editing reactions which ensure that an amino acid is stably attached to its corresponding transfer RNA (tRNA). Previous studies have not shown whether the tRNA nucleotides needed for effecting translational editing are the same as or distinct from those required for aminoacylation, but several considerations have suggested that they are the same. Here, designed tRNAs that are highly active for aminoacylation but are not active in translational editing are presented. The editing reaction can be controlled by manipulation of nucleotides at the corner of the L-shaped tRNA. In contrast, these manipulations do not affect aminoacylation. These results demonstrate the segregation of nucleotide determinants for the editing and aminoacylation functions of tRNA.
Assuntos
Edição de RNA , RNA de Transferência/metabolismo , Acetilação , Sequência de Bases , Sítios de Ligação , Clonagem Molecular , Escherichia coli , Dados de Sequência Molecular , Conformação de Ácido Nucleico , RNA de Transferência de Isoleucina/química , RNA de Transferência de Isoleucina/metabolismo , RNA de Transferência de Valina/química , RNA de Transferência de Valina/metabolismoRESUMO
A subline of U937 cells (U937D) was obtained in which creatine kinase B (CK-B) messenger RNA was present and bound to ribosomes, but CK activity was undetectable. Transformation of U937D cells with retrovirus vectors that contain the 3' untranslated region (3' UTR) of CK-B messenger RNA exhibited CK activity with no change in abundance of CK-B mRNA. The 3' UTR formed a complex in vitro with a component of S100 extracts from wild-type cells. This binding activity was not detectable in S100 extracts from cells that expressed CK activity after transformation with the 3' UTR-containing vector. These results suggest that translation of CK-B is repressed by binding of a soluble factor or factors to the 3' UTR.
Assuntos
Creatina Quinase/genética , Regulação da Expressão Gênica , Biossíntese de Proteínas , RNA Mensageiro/genética , Linhagem Celular , Clonagem Molecular , Humanos , Hipoxantina Fosforribosiltransferase/genética , Polirribossomos/metabolismoRESUMO
An acceptor stem G3.U70 base pair is a major determinant of the identity of an alanine transfer RNA. Hairpin helices and RNA duplexes consisting of complementary single strands are aminoacylated with alanine if they contain G3.U70. Chemical synthesis of RNA duplexes enabled the introduction of base analogs that tested the role of specific functional groups in the major and minor grooves of the RNA helix. The results of these experiments indicate that an unpaired guanine 2-amino group at a specific position in the minor groove of an RNA helix marks a molecule for aminoacylation with alanine.
Assuntos
Alanina-tRNA Ligase/metabolismo , RNA de Transferência de Alanina/metabolismo , Acilação , Sequência de Bases , Técnicas In Vitro , Dados de Sequência Molecular , Estrutura Molecular , Conformação de Ácido Nucleico , Oligonucleotídeos/química , RNA de Transferência de Alanina/química , Relação Estrutura-AtividadeRESUMO
Few and limited amino acid sequence homologies have been found among eight bacterial aminoacyl transfer RNA (tRNA) synthetases whose primary structures are known. The entire 939-amino acid primary structure of Escherichia coli isoleucyl-tRNA synthetase is now reported. In a sequence of 11 consecutive amino acids matching a sequence in E. coli methionyl-tRNA synthetase, there are ten identical residues and one conservative change. This is the strongest homology recorded between any two aminoacyl tRNA synthetases. This part of the methionine enzyme's three-dimensional structure has been determined, and it occurs in a mononucleotide binding fold; a close three-dimensional structural homology of this part of the enzyme with Bacillus stearothermophilus tyrosyl-tRNA synthetase has also been reported. The three synthetases probably fold identically in this region.
Assuntos
Aminoacil-tRNA Sintetases , Sequência de Aminoácidos , Escherichia coli/enzimologia , Geobacillus stearothermophilus/enzimologia , Isoleucina-tRNA Ligase , Metionina tRNA Ligase , Conformação ProteicaRESUMO
Aminoacyl transfer RNA (tRNA) synthetases establish the rules of the genetic code by catalyzing the aminoacylation of tRNAs. For some synthetases, accuracy depends critically on an editing function at a site distinct from the aminoacylation site. Mutants of Escherichia coli that incorrectly charge tRNA(Val) with cysteine were selected after random mutagenesis of the whole chromosome. All mutations obtained were located in the editing site of valyl-tRNA synthetase. More than 20% of the valine in cellular proteins from such an editing mutant organism could be replaced with the noncanonical aminobutyrate, sterically similar to cysteine. Thus, the editing function may have played a central role in restricting the genetic code to 20 amino acids. Disabling this editing function offers a powerful approach for diversifying the chemical composition of proteins and for emulating evolutionary stages of ambiguous translation.
Assuntos
Aminobutiratos/metabolismo , Escherichia coli/genética , Código Genético , Biossíntese de Proteínas , RNA de Transferência de Valina/metabolismo , Valina-tRNA Ligase/metabolismo , Alelos , Sequência de Aminoácidos , Substituição de Aminoácidos , Sítios de Ligação , Códon , Cisteína/metabolismo , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/metabolismo , Dados de Sequência Molecular , Mutagênese , Fenótipo , RNA Bacteriano/genética , RNA Bacteriano/metabolismo , Supressão Genética , Treonina/metabolismo , Aminoacilação de RNA de Transferência , Valina/metabolismo , Valina-tRNA Ligase/química , Valina-tRNA Ligase/genéticaRESUMO
High-fidelity transfers of genetic information in the central dogma can be achieved by a reaction called editing. The crystal structure of an enzyme with editing activity in translation is presented here at 2.5 angstroms resolution. The enzyme, isoleucyl-transfer RNA synthetase, activates not only the cognate substrate L-isoleucine but also the minimally distinct L-valine in the first, aminoacylation step. Then, in a second, "editing" step, the synthetase itself rapidly hydrolyzes only the valylated products. For this two-step substrate selection, a "double-sieve" mechanism has already been proposed. The present crystal structures of the synthetase in complexes with L-isoleucine and L-valine demonstrate that the first sieve is on the aminoacylation domain containing the Rossmann fold, whereas the second, editing sieve exists on a globular beta-barrel domain that protrudes from the aminoacylation domain.
Assuntos
Isoleucina-tRNA Ligase/química , Isoleucina/metabolismo , Valina/metabolismo , Monofosfato de Adenosina , Sítios de Ligação , Cristalografia por Raios X , Escherichia coli/enzimologia , Ligação de Hidrogênio , Hidrólise , Isoleucina-tRNA Ligase/metabolismo , Modelos Químicos , Modelos Moleculares , Dados de Sequência Molecular , Mutagênese , Conformação Proteica , Dobramento de Proteína , Estrutura Secundária de Proteína , RNA de Transferência de Isoleucina/metabolismo , Especificidade por Substrato , Thermus thermophilus/enzimologia , Aminoacilação de RNA de TransferênciaRESUMO
The recognition of transfer RNAs (tRNAs) by aminoacyl tRNA synthetases establishes the connection between amino acids and trinucleotides. However, for E. coli alanine tRNA the trinucleotide sequence which specifies alanine is not important for recognition. Instead a single base pair is a major determinant for the identity of this tRNA. Even a synthetic RNA microhelix with seven base pairs can be aminoacylated if it includes the major determinant.
Assuntos
Alanina/metabolismo , Anticódon , Escherichia coli/genética , RNA de Transferência de Alanina/genética , RNA de Transferência Aminoácido-Específico/genética , RNA de Transferência , Aminoacil-tRNA Sintetases/metabolismo , Sequência de Bases , Evolução Biológica , Cinética , Dados de Sequência Molecular , Conformação de Ácido NucleicoRESUMO
Aminoacylation of tRNAs, catalyzed by 20 aminoacyl-tRNA synthetases, is responsible for establishing the genetic code. The enzymes are divided into two classes on the basis of the architectures of their active sites. Members of the two classes also differ in that they bind opposite sides of the tRNA acceptor stem. Importantly, specific pairs of synthetases--one from each class--can be docked simultaneously onto the acceptor stem. This article relates these specific pairings to the organization of the table of codons that defines the universal genetic code.
Assuntos
Aminoacil-tRNA Sintetases/genética , Código Genético , Aminoacil-tRNA Sintetases/química , Aminoacil-tRNA Sintetases/classificação , Animais , Domínio Catalítico , Códon/genética , Evolução Molecular , Humanos , Modelos Moleculares , Conformação de Ácido Nucleico , Conformação Proteica , RNA de Transferência/químicaRESUMO
The universal genetic code is determined by the aminoacylation of tRNAs. In spite of the universality of the code, there are barriers to aminoacylation across taxonomic domains. These barriers are thought to correlate with the co-segregation of sequences of synthetases and tRNAs into distinct taxonomic domains. By contrast, we show here examples of eukaryote-like synthetases that are found in certain prokaryotes. The associated tRNAs have retained their prokaryote-like character in each instance. Thus, co-segregation of domain-specific synthetases and tRNAs does not always occur. Instead, synthetases make adaptations of tRNA-protein contacts to cross taxonomic domains.