scholarly journals Identification and characterization of two types of amino acid-regulated acetyltransferases in actinobacteria

2017 ◽  
Vol 37 (4) ◽  
Author(s):  
Yu-Xing Lu ◽  
Xin-Xin Liu ◽  
Wei-Bing Liu ◽  
Bang-Ce Ye
Keyword(s):  
Amino Acid ◽  
Feedback Regulation ◽  
Protein Acetylation ◽  
Post Translational Modifications ◽  
Act Domain ◽  
Amino Acid Binding ◽  
Amino Acid Sensing ◽  
And Function ◽  
Future Work ◽  
The Relationship

Abstract One hundred and fifty GCN5-like acetyltransferases with amino acid-binding (ACT)-GCN5-related N-acetyltransferase (GNAT) domain organization have been identified in actinobacteria. The ACT domain is fused to the GNAT domain, conferring amino acid-induced allosteric regulation to these protein acetyltransferases (Pat) (amino acid sensing acetyltransferase, (AAPatA)). Members of the AAPatA family share similar secondary structure and are divided into two groups based on the allosteric ligands of the ACT domain: the asparagine (Asn)-activated PatA and the cysteine (Cys)-activated PatA. The former are mainly found in Streptomyces; the latter are distributed in other actinobacteria. We investigated the effect of Asn and Cys on the acetylation activity of Sven_0867 (SvePatA, from Streptomyces venezuelae DSM 40230) and Amir_5672 (AmiPatA, from Actinosynnema mirum strain DSM 43827), respectively, as well as the relationship between the structure and function of these enzymes. These findings indicate that the activity of PatA and acetylation level of proteins may be closely correlated with intracellular concentrations of Asn and Cys in actinobacteria. Amino acid-sensing signal transduction in acetyltransferases may be a mechanism that regulates protein acetylation in response to nutrient availability. Future work examining the relationship between protein acetylation and amino acid metabolism will broaden our understanding of post-translational modifications (PTMs) in feedback regulation.

scholarly journals Protein acetylation: an important mechanism in actinobacteria

2018 ◽  
Vol 38 (2) ◽  
Author(s):  
Huaidong Zhang ◽  
Ximing Xu
Keyword(s):  
Amino Acid ◽  
Structure And Function ◽  
Lysine Acetylation ◽  
Protein Acetylation ◽  
Research Article ◽  
Act Domain ◽  
Amino Acid Binding ◽  
Amino Acid Sensing ◽  
And Function ◽  
The Relationship

This is a commentary on the research article by Lu et al. recently published in Bioscience Reports. The GCN5-like acetyltransferases with amino acid-binding (ACT)-GCN5-related N-acetyltransferase (GNAT) domain organization have been identified in actinobacteria by Lu et al. (2017). The ACT domain is fused to the GNAT domain, conferring amino acid-induced allosteric regulation to these protein acetyltransferases (Pat) (amino acid sensing acetyltransferase (AAPatA)). Members of the AAPatA family share similar secondary structure and are divided into two groups based on the allosteric ligands of the ACT domain: the asparagine (Asn)-activated PatA and the cysteine (Cys)-activated PatA. The former are mainly found in Streptomyces; the latter are distributed in other actinobacteria. The authors investigated the effect of Asn and Cys on the acetylation activity of Sven_0867 (SvePatA, from Streptomyces venezuelae DSM 40230) and Amir_5672 (AmiPatA, from Actinosynnema mirum strain DSM 43827), respectively, as well as the relationship between the structure and function of these enzymes. Research history and progress on acetyltransferases and lysine acetylation of proteins were discussed. The activity of PatA and acetylation level of proteins may be closely correlated with intracellular concentrations of Asn and Cys in actinobacteria.

Structure and function of voltage-dependent sodium channels: comparison of brain II and cardiac isoforms

1996 ◽  
Vol 76 (3) ◽  
pp. 887-926 ◽  
Author(s):  
H. A. Fozzard ◽  
D. A. Hanck
Keyword(s):  
Amino Acid ◽  
Three Dimensional ◽  
Point Mutations ◽  
Amino Acid Sequences ◽  
Na Channel ◽  
Na Channels ◽  
Voltage Dependent ◽  
And Function ◽  
Relationship Of ◽  
The Relationship

Cardiac and nerve Na channels have broadly similar functional properties and amino acid sequences, but they demonstrate specific differences in gating, permeation, ionic block, modulation, and pharmacology. Resolution of three-dimensional structures of Na channels is unlikely in the near future, but a number of amino acid sequences from a variety of species and isoforms are known so that channel differences can be exploited to gain insight into the relationship of structure to function. The combination of molecular biology to create chimeras and channels with point mutations and high-resolution electrophysiological techniques to study function encourage the idea that predictions of structure from function are possible. With the goal of understanding the special properties of the cardiac Na channel, this review examines the structural (sequence) similarities between the cardiac and nerve channels and considers what is known about the relationship of structure to function for voltage-dependent Na channels in general and for the cardiac Na channels in particular.

scholarly journals Amino acid-sensing mTOR signaling is involved in modulation of lipolysis by chronic insulin treatment in adipocytes

2009 ◽  
Vol 296 (4) ◽  
pp. E862-E868 ◽  
Author(s):  
Chongben Zhang ◽  
Mee-Sup Yoon ◽  
Jie Chen
Keyword(s):  
Amino Acid ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Pathway ◽  
Phosphatidylinositol 3 Kinase ◽  
Insulin Effect ◽  
Triacylglycerol Hydrolase ◽  
High Insulin ◽  
Amino Acid Sensing ◽  
The Relationship ◽  
Stimulation Of

Chronically high insulin levels and increased circulating free fatty acids released from adipose tissue through lipolysis are two features associated with insulin resistance. The relationship between chronic insulin exposure and adipocyte lipolysis has been unclear. In the present study we found that chronic insulin exposure in 3T3-L1 adipocytes, as well as in mouse primary adipocytes, increased basal lipolysis rates. This effect of insulin on lipolysis was only observed when the mammalian target of rapamycin (mTOR) pathway was inhibited by rapamycin in the adipocytes. In addition, amino acid deprivation in adipocytes phenocopied the effect of rapamycin in permitting the stimulation of lipolysis by chronic insulin exposure. The phosphatidylinositol 3-kinase-Akt pathway does not appear to be involved in this insulin effect. Furthermore, we found that triacylglycerol hydrolase (TGH) activity was required for the stimulation of lipolysis by combined exposure to insulin and rapamycin. Therefore, we propose that nutrient sufficiency, mediated by an mTOR pathway, suppresses TGH-dependent lipolysis stimulated by chronic insulin exposure in adipocytes.

scholarly journals Editorial—Role of DNA Methyltransferases in the Epigenome

Genes ◽  
2019 ◽  
Vol 10 (8) ◽  
pp. 574 ◽  
Author(s):  
Jeltsch ◽  
Gowher
Keyword(s):  
Dna Methylation ◽  
Phenotypic Diversity ◽  
Rapid Development ◽  
Cell Types ◽  
Dna Methyltransferases ◽  
Mammalian Development ◽  
Exciting Field ◽  
Post Translational Modifications ◽  
And Function ◽  
Future Work

DNA methylation, a modification found in most species, regulates chromatin functions in conjunction with other epigenome modifications, such as histone post-translational modifications and non-coding RNAs. In mammals, DNA methylation has essential roles in development by orchestrating the generation and maintenance of the phenotypic diversity of human cell types. This Special Issue of Genes contains eight review articles, which cover several aspects of epigenome regulation by DNA methyltransferases (DNMTs), the enzymes responsible for the introduction of DNA methylation. The manuscripts present the most recent advances regarding the structure and function of DNMTs, their targeting and regulation by interacting factors and chromatin modifications, and the roles of DNMTs in mammalian development and human diseases. However, many aspects of these important enzymes are still insufficiently understood. Potential directions of future work are the regulation of DNMTs by post-translational modifications and their connection to cellular signaling and second messenger cascades on one hand and to large multifactorial epigenetic chromatin circuits on the other. Additionally, technical advancements, including the availability of designer nucleosomes and the rapid development of cryo-electron microscopy are expected to trigger breakthrough discoveries in this exciting field.

scholarly journals The Venus Fly Trap Domain of the Extracellular Ca2+-sensing Receptor Is Required for l-Amino Acid Sensing

2004 ◽  
Vol 279 (50) ◽  
pp. 51739-51744 ◽  
Author(s):  
Hee-Chang Mun ◽  
Alison H. Franks ◽  
Emma L. Culverston ◽  
Karen Krapcho ◽  
Edward F. Nemeth ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Binding Site ◽  
Hek293 Cells ◽  
Transmembrane Region ◽  
Rich Region ◽  
Metabotropic Glutamate ◽  
C Terminus ◽  
Amino Acid Binding ◽  
Amino Acid Sensing

We previously demonstrated that the human calcium-sensing receptor (CaR) is allosterically activated byl-amino acids (Conigrave, A. D., Quinn, S. J., and Brown, E. M. (2000)Proc. Natl. Acad. Sci. U. S. A.97, 4814–4819). However, the domain-based location of amino acid binding has been uncertain. We now show that the Venus Fly Trap (VFT) domain of CaR, but none of its other major domains, is required for amino acid sensing. Several constructs were informative when expressed in HEK293 cells. First, the wild-type CaR exhibited allosteric activation byl-amino acids as previously observed. Second, two CaR-mGlu chimeric receptor constructs that retained the VFT domain of CaR, one containing the extracellular Cys-rich region of CaR and the other containing the Cys-rich region of the rat metabotropic glutamate type-1 (mGlu-1) receptor, together with the rat mGlu-1 transmembrane region and C-terminal tail, retained amino acid sensing. Third, a CaR lacking residues 1–599 of the N-terminal extracellular head but retaining an intact CaR transmembrane region and a functional but truncated C terminus (headless-T903 CaR) failed to respond tol-amino acids but retained responsiveness to the type-II calcimimetic NPS R-467. Finally, a T903 CaR control that retained an intact N terminus also retainedl-amino acid sensing. Taken together, the data indicate that the VFT domain of CaR is necessary forl-amino acid sensing and are consistent with the hypothesis that the VFT domain is the site ofl-amino acid binding. The findings support the concept that the mGlu-1 amino acid binding site forl-glutamate is conserved as anl-amino acid binding site in its homolog, the CaR.

scholarly journals The contribution of mutant amino acids to alloantigenicity.

1989 ◽  
Vol 170 (3) ◽  
pp. 739-750 ◽  
Author(s):  
J Bill ◽  
F Ronchese ◽  
R N Germain ◽  
E Palmer
Keyword(s):  
Amino Acid ◽  
Structural Model ◽  
Structure And Function ◽  
Single Amino Acid ◽  
Amino Acid Substitutions ◽  
Beta Chain ◽  
Alpha Helices ◽  
The Third ◽  
And Function ◽  
The Relationship

The I-Abm12 mutation has been used extensively to study the relationship between structure and function of murine class II major histocompatibility molecules. I-Abm12 differs from I-Ab by three amino acid replacements in the A beta chain, and the proposed structural model of the I-Abm12 molecule places these three amino acid substitutions along one of the alpha-helices where they may affect both antigen and TCR binding. Two of the substitutions, Ile----Phe67 and Thr----Lys71, are thought to point into the binding site, whereas the third substitution, Arg----Gln70, is thought to point up and hence, be available for binding to the TCR. These predicted orientations are consistent with serologic analysis of the bm12 molecule, which demonstrates that residue 70 is uniquely accessible to mAbs distinguishing I-Ab from I-Abm12. In this study we have determined the influence of each of these amino acid substitutions on the ability of the resulting molecules to stimulate a panel of I-Abm12 (allo) reactive T cell hybridomas. Our experiments indicate that reversion of the amino acid at position 70 from Gln (I-Abm12) to Arg (I-Ab) interferes with allorecognition by 33 of 35 I-Abm12-reactive hybridomas. On the other hand, many hybrids can tolerate amino acid substitutions at positions 67 or 71. Single amino acid substitutions at position 67, 70, or 71 are recognized by only a minority of I-Abm12-specific hybrids and usually the reactivity is greatly diminished. These data are most consistent with the idea that the amino acid at position 70 directly interacts with the TCR during allorecognition. The additional effects of residues 67 and 71 are consistent with a contribution by bound peptide to the allorecognition process.

scholarly journals The relationship between sternum variation and mode of locomotion in birds

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Talia M. Lowi-Merri ◽  
Roger B. J. Benson ◽  
Santiago Claramunt ◽  
David C. Evans
Keyword(s):  
Body Shape ◽  
Explanatory Power ◽  
Critical Element ◽  
Form And Function ◽  
Avian Flight ◽  
Flight Muscles ◽  
Ecological Importance ◽  
And Function ◽  
Future Work ◽  
The Relationship

Abstract Background The origin of powered avian flight was a locomotor innovation that expanded the ecological potential of maniraptoran dinosaurs, leading to remarkable variation in modern birds (Neornithes). The avian sternum is the anchor for the major flight muscles and, despite varying widely in morphology, has not been extensively studied from evolutionary or functional perspectives. We quantify sternal variation across a broad phylogenetic scope of birds using 3D geometric morphometrics methods. Using this comprehensive dataset, we apply phylogenetically informed regression approaches to test hypotheses of sternum size allometry and the correlation of sternal shape with both size and locomotory capabilities, including flightlessness and the highly varying flight and swimming styles of Neornithes. Results We find evidence for isometry of sternal size relative to body mass and document significant allometry of sternal shape alongside important correlations with locomotory capability, reflecting the effects of both body shape and musculoskeletal variation. Among these, we show that a large sternum with a deep or cranially projected sternal keel is necessary for powered flight in modern birds, that deeper sternal keels are correlated with slower but stronger flight, robust caudal sternal borders are associated with faster flapping styles, and that narrower sterna are associated with running abilities. Correlations between shape and locomotion are significant but show weak explanatory power, indicating that although sternal shape is broadly associated with locomotory ecology, other unexplored factors are also important. Conclusions These results display the ecological importance of the avian sternum for flight and locomotion by providing a novel understanding of sternum form and function in Neornithes. Our study lays the groundwork for estimating the locomotory abilities of paravian dinosaurs, the ancestors to Neornithes, by highlighting the importance of this critical element for avian flight, and will be useful for future work on the origin of flight along the dinosaur-bird lineage.

scholarly journals Mutually exclusive locales for N-linked glycans and disorder in glycoproteins

2018 ◽  
Author(s):  
Alvina Singh ◽  
Indu Kumari ◽  
Dharma Pally ◽  
Shyamili Goutham ◽  
Sujasha Ghosh ◽  
...  
Keyword(s):  
Amino Acid ◽  
Protein Stability ◽  
Amino Acid Residue ◽  
Tertiary Structure ◽  
Amino Acid Residues ◽  
Mutual Exclusivity ◽  
Post Translational Modifications ◽  
Phylogenetic Conservation ◽  
And Function ◽  
Disordered Regions

AbstractSeveral post-translational modifications of proteins lie within regions of disorder, stretches of amino acid residues that exhibit a dynamic tertiary structure and resist crystallization. Such localization has been proposed to expand the binding versatility of the disordered regions, and hence, the repertoire of interacting partners for the proteins. However, investigating a dataset of 500 human N-linked glycoproteins, we observed that the sites of N-linked glycosylations, or N-glycosites, lay predominantly within the regions of predicted order rather than their unstructured counterparts. This mutual exclusivity between disordered stretches and N-glycosites could not be reconciled merely through asymmetry in distribution of asparagines, serines or threonines residues, which comprise the minimum-required signature for conjugation by N-linked glycans, but rather by a contextual enrichment of these residues next to each other within the ordered portions. In fact, N-glycosite neighborhoods and disordered stretches showed distinct sets of enriched residues suggesting their individualized roles in protein phenotype. N-glycosite neighborhood residues also showed higher phylogenetic conservation than disordered stretches within amniote orthologs of glycoproteins. However, a universal search for residue-combinations that are putatively domain-constitutive ranked the disordered regions higher than the N-glycosite neighborhoods. We propose that amino acid residue-combinations bias the permissivity for N-glycoconjugation within ordered regions, so as to balance the tradeoff between the evolution of protein stability, and function, contributed by the N-linked glycans and disordered regions respectively.

scholarly journals The Structure ofampGGene inPseudomonas aeruginosaand Its Effect on Drug Resistance

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Qingli Chang ◽  
Chongyang Wu ◽  
Chaoqing Lin ◽  
Peizhen Li ◽  
Kaibo Zhang ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Inhibitory Concentration ◽  
Normal Function ◽  
Structure And Function ◽  
Clinical Isolates ◽  
Site Specific ◽  
Directed Mutation ◽  
And Function ◽  
The Relationship

In order to study the relationship between the structure and function of AmpG, structure, site-specific mutation, and gene complementary experiments have been performed against the clinical isolates ofPseudomonas aeruginosa. We found that there are 51 nucleotide variations at 34 loci over theampGgenes from 24 of 35P. aeruginosastrains detected, of which 7 nucleotide variations resulted in amino acid change. TheampGvariants with the changed nucleotides (amino acids) could complement the function ofampGdeleted PA01 (PA01ΔG). The ampicillin minimum inhibitory concentration (MIC) of PA01ΔG complemented with 32ampGvariants was up to 512 μg/ml, similar to the original PA01 (P. aeruginosa PA01). Furthermore, site-directed mutation of two conservative amino acids (I53 and W90) showed that when I53 was mutated to 53S or 53T (I53S or I53T), the ampicillin MIC level dropped drastically, and the activity of AmpCβ-lactamase decreased as well. By contrast, the ampicillin MIC and the activity of AmpCβ-lactamase remained unchanged for W90R and W90S mutants. Our studies demonstrated that although nucleotide variations occurred in most of theampGgenes, the structure of AmpG protein in clinical isolates is stable, and conservative amino acid is necessary to maintain normal function of AmpG.

Genetic dissection of Ragulator structure and function in amino acid-dependent regulation of mTORC1

2020 ◽  
Vol 168 (6) ◽  
pp. 621-632
Author(s):  
Shigeyuki Nada ◽  
Masato Okada
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Feedback Regulation ◽  
Genetic Dissection ◽  
Independent Manner ◽  
Negative Feedback Regulation ◽  
Rag Gtpases ◽  
And Function ◽  
Mtorc1 Activation ◽  
Membrane Scaffold

Abstract Ragulator is a heteropentameric protein complex consisting of two roadblock heterodimers wrapped by the membrane anchor p18/Lamtor1. The Ragulator complex functions as a lysosomal membrane scaffold for Rag GTPases to recruit and activate mechanistic target of rapamycin complex 1 (mTORC1). However, the roles of Ragulator structure in the regulation of mTORC1 function remain elusive. In this study, we disrupted Ragulator structure by directly anchoring RagC to lysosomes and monitored the effect on amino acid-dependent mTORC1 activation. Expression of lysosome-anchored RagC in p18-deficient cells resulted in constitutive lysosomal localization and amino acid-independent activation of mTORC1. Co-expression of Ragulator in this system restored the amino acid dependency of mTORC1 activation. Furthermore, ablation of Gator1, a suppressor of Rag GTPases, induced amino acid-independent activation of mTORC1 even in the presence of Ragulator. These results demonstrate that Ragulator structure is essential for amino acid-dependent regulation of Rag GTPases via Gator1. In addition, our genetic analyses revealed new roles of amino acids in the regulation of mTORC1 as follows: amino acids could activate a fraction of mTORC1 in a Rheb-independent manner, and could also drive negative-feedback regulation of mTORC1 signalling via protein phosphatases. These intriguing findings contribute to our overall understanding of the regulatory mechanisms of mTORC1 signalling.

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