当前位置： SCI文献检索 > Computational and Structural Biotechnology Journal期刊下所有文献 > Experimental and computational analysis of biased agonism on full-length and a C-terminally truncated adenosine A2A receptor.

Experimental and computational analysis of biased agonism on full-length and a C-terminally truncated adenosine A2A receptor.

Abstract：

:Biased agonism, the ability of agonists to differentially activate downstream signaling pathways by stabilizing specific receptor conformations, is a key issue for G protein-coupled receptor (GPCR) signaling. The C-terminal domain might influence this functional selectivity of GPCRs as it engages G proteins, GPCR kinases, β-arrestins, and several other proteins. Thus, the aim of this paper is to compare the agonist-dependent selectivity for intracellular pathways in a heterologous system expressing the full-length (A2AR) and a C-tail truncated (A2AΔ40R lacking the last 40 amino acids) adenosine A2A receptor, a GPCR that is already targeted in Parkinson's disease using a first-in-class drug. Experimental data such as ligand binding, cAMP production, β-arrestin recruitment, ERK1/2 phosphorylation and dynamic mass redistribution assays, which correspond to different aspects of signal transduction, were measured upon the action of structurally diverse compounds (the agonists adenosine, NECA, CGS-21680, PSB-0777 and LUF-5834 and the SCH-58261 antagonist) in cells expressing A2AR and A2AΔ40R. The results show that taking cAMP levels and the endogenous adenosine agonist as references, the main difference in bias was obtained with PSB-0777 and LUF-5834. The C-terminus is dispensable for both G-protein and β-arrestin recruitment and also for MAPK activation. Unrestrained molecular dynamics simulations, at the μs timescale, were used to understand the structural arrangements of the binding cavity, triggered by these chemically different agonists, facilitating G protein binding with different efficacy.

journal_name

Comput Struct Biotechnol J

journal_title

Computational and structural biotechnology journal

authors

Navarro G,Gonzalez A,Campanacci S,Rivas-Santisteban R,Reyes-Resina I,Casajuana-Martin N,Cordomí A,Pardo L,Franco R

doi

10.1016/j.csbj.2020.09.028

subject

Has Abstract

pub_date

2020-09-24 00:00:00

pages

2723-2732

issn

2001-0370

pii

S2001-0370(20)30412-8

journal_volume

18

pub_type

杂志文章

相关文献

Computational and Structural Biotechnology Journal文献大全
  • Structural insights into the mechanism of RNA recognition by the N-terminal RNA-binding domain of the SARS-CoV-2 nucleocapsid phosphoprotein.

    abstract：:The emergence of recent SARS-CoV-2 has become a global health issue. This single-stranded positive-sense RNA virus is continuously spreading with increasing morbidities and mortalities. The proteome of this virus contains four structural and sixteen nonstructural proteins that ensure the replication of the virus in th...

    journal_title：Computational and structural biotechnology journal

    pub_type： 杂志文章

    doi：10.1016/j.csbj.2020.08.006

    authors： Khan A,Tahir Khan M,Saleem S,Junaid M,Ali A,Shujait Ali S,Khan M,Wei DQ

    更新日期：2020-01-01 00:00:00

  • Stage-specific control of stem cell niche architecture in the Drosophila testis by the posterior Hox gene Abd-B.

    abstract：:A fundamental question in biology is how complex structures are maintained after their initial specification. We address this question by reviewing the role of the Hox gene Abd-B in Drosophila testis organogenesis, which proceeds through embryonic, larval and pupal stages to reach maturation in adult stages. The data ...

    journal_title：Computational and structural biotechnology journal

    pub_type： 杂志文章,评审

    doi：10.1016/j.csbj.2015.01.001

    authors： Papagiannouli F,Lohmann I

    更新日期：2015-01-21 00:00:00

  • The era of big data: Genome-scale modelling meets machine learning.

    abstract：:With omics data being generated at an unprecedented rate, genome-scale modelling has become pivotal in its organisation and analysis. However, machine learning methods have been gaining ground in cases where knowledge is insufficient to represent the mechanisms underlying such data or as a means for data curation prio...

    journal_title：Computational and structural biotechnology journal

    pub_type： 杂志文章,评审

    doi：10.1016/j.csbj.2020.10.011

    authors： Antonakoudis A,Barbosa R,Kotidis P,Kontoravdi C

    更新日期：2020-10-16 00:00:00

  • Causal inference for the effect of environmental chemicals on chronic kidney disease.

    abstract：:The impacts of environmental chemicals on the decline of kidney function have been suggested by a limited number of statistical and animal studies. Thus, those exposures may be modifiable risk factors for chronic kidney disease. Some of the chemicals, such as Perfluoroalkyl acid (PFA), are pervasive throughout our env...

    journal_title：Computational and structural biotechnology journal

    pub_type： 杂志文章

    doi：10.1016/j.csbj.2019.12.001

    authors： Zhao J,Hinton P,Chen J,Jiang J

    更新日期：2019-12-17 00:00:00

  • Reactive oxygen species: A generalist in regulating development and pathogenicity of phytopathogenic fungi.

    abstract：:Reactive oxygen species (ROS) are small molecules with high oxidative activity, and are usually produced as byproducts of metabolic processes in organisms. ROS play an important role during the interaction between plant hosts and pathogenic fungi. Phytopathogenic fungi have evolved sophisticated ROS producing and scav...

    journal_title：Computational and structural biotechnology journal

    pub_type： 杂志文章,评审

    doi：10.1016/j.csbj.2020.10.024

    authors： Zhang Z,Chen Y,Li B,Chen T,Tian S

    更新日期：2020-11-04 00:00:00

  • Immunopathology, host-virus genome interactions, and effective vaccine development in SARS-CoV-2.

    abstract：:Coronaviruses are a group of enveloped RNA viruses that are diversely found in humans and now declared a global pandemic by the World Health Organization in March 2020. The population's susceptibility to these highly pathogenic coronaviruses has contributed to large outbreaks, evolved into public health events, and ra...

    journal_title：Computational and structural biotechnology journal

    pub_type： 杂志文章,评审

    doi：10.1016/j.csbj.2020.11.011

    authors： Singh DD,Han I,Choi EH,Yadav DK

    更新日期：2020-01-01 00:00:00

  • Asymmetric Spontaneous Intercalation of Lutein into a Phospholipid Bilayer, a Computational Study.

    abstract：:Lutein, a hydroxylated carotenoid, is a pigment synthesised by plants and bacteria. Animals are unable to synthesise lutein, nevertheless, it is present in animal tissues, where its only source is dietary intake. Both in plants and animals, carotenoids are associated mainly with membranes where they carry out importan...

    journal_title：Computational and structural biotechnology journal

    pub_type： 杂志文章

    doi：10.1016/j.csbj.2019.04.001

    authors： Makuch K,Markiewicz M,Pasenkiewicz-Gierula M

    更新日期：2019-04-06 00:00:00

  • Experimental determination and data-driven prediction of homotypic transmembrane domain interfaces.

    abstract：:Interactions between their transmembrane domains (TMDs) frequently support the assembly of single-pass membrane proteins to non-covalent complexes. Yet, the TMD-TMD interactome remains largely uncharted. With a view to predicting homotypic TMD-TMD interfaces from primary structure, we performed a systematic analysis o...

    journal_title：Computational and structural biotechnology journal

    pub_type： 杂志文章

    doi：10.1016/j.csbj.2020.09.035

    authors： Xiao Y,Zeng B,Berner N,Frishman D,Langosch D,George Teese M

    更新日期：2020-10-07 00:00:00

  • AUDACITY: A comprehensive approach for the detection and classification of Runs of Homozygosity in medical and population genomics.

    abstract：:Runs of Homozygosity (RoHs) are popular among geneticists as the footprint of demographic processes, evolutionary forces and inbreeding in shaping our genome, and are known to confer risk of Mendelian and complex diseases. Notwithstanding growing interest in their study, there is unmet need for reliable and rapid meth...

    journal_title：Computational and structural biotechnology journal

    pub_type： 杂志文章

    doi：10.1016/j.csbj.2020.07.003

    authors： Magi A,Giangregorio T,Semeraro R,Carangelo G,Palombo F,Romeo G,Seri M,Pippucci T

    更新日期：2020-07-14 00:00:00

  • The ecogenomics of dsDNA bacteriophages in feces of stabled and feral horses.

    abstract：:The viromes of the mammalian lower gut were shown to be heavily dominated by bacteriophages; however, only for humans were the composition and intervariability of the bacteriophage communities studied in depth. Here we present an ecogenomics survey of dsDNA bacteriophage diversity in the feces of horses (Equus caballu...

    journal_title：Computational and structural biotechnology journal

    pub_type： 杂志文章

    doi：10.1016/j.csbj.2020.10.036

    authors： Babenko VV,Millard A,Kulikov EE,Spasskaya NN,Letarova MA,Konanov DN,Belalov IS,Letarov AV

    更新日期：2020-11-10 00:00:00

  • In Silico Prediction of Large-Scale Microbial Production Performance: Constraints for Getting Proper Data-Driven Models.

    abstract：:Industrial bioreactors range from 10.000 to 700.000 L and characteristically show different zones of substrate availabilities, dissolved gas concentrations and pH values reflecting physical, technical and economic constraints of scale-up. Microbial producers are fluctuating inside the bioreactors thereby experiencing ...

    journal_title：Computational and structural biotechnology journal

    pub_type： 杂志文章,评审

    doi：10.1016/j.csbj.2018.06.002

    authors： Zieringer J,Takors R

    更新日期：2018-07-06 00:00:00

  • Multi-population cohort meta-analysis of human intestinal microbiota in early life reveals the existence of infant community state types (ICSTs).

    abstract：:Appropriate development of the intestinal microbiota during infancy is known to be important for human health. In fact, aberrant alterations of the microbial composition during childhood may cause short- and/or long-term negative health effects. Many factors influence the initial assembly and subsequent progression of...

    journal_title：Computational and structural biotechnology journal

    pub_type： 杂志文章

    doi：10.1016/j.csbj.2020.08.028

    authors： Mancabelli L,Tarracchini C,Milani C,Lugli GA,Fontana F,Turroni F,van Sinderen D,Ventura M

    更新日期：2020-09-15 00:00:00

  • Learning distributed representations of RNA and protein sequences and its application for predicting lncRNA-protein interactions.

    abstract：:The long noncoding RNAs (lncRNAs) are ubiquitous in organisms and play crucial role in a variety of biological processes and complex diseases. Emerging evidences suggest that lncRNAs interact with corresponding proteins to perform their regulatory functions. Therefore, identifying interacting lncRNA-protein pairs is t...

    journal_title：Computational and structural biotechnology journal

    pub_type： 杂志文章

    doi：10.1016/j.csbj.2019.11.004

    authors： Yi HC,You ZH,Cheng L,Zhou X,Jiang TH,Li X,Wang YB

    更新日期：2019-11-30 00:00:00

  • Transcriptomics in the tropics: Total RNA-based profiling of Costa Rican bromeliad-associated communities.

    abstract：:RNA-Seq was used to examine the microbial, eukaryotic, and viral communities in water catchments ('tanks') formed by tropical bromeliads from Costa Rica. In total, transcripts with taxonomic affiliation to a wide array of bacteria, archaea, and eukaryotes, were observed, as well as RNA-viruses that appeared related to...

    journal_title：Computational and structural biotechnology journal

    pub_type： 杂志文章

    doi：10.1016/j.csbj.2014.12.001

    authors： Goffredi SK,Jang GE,Haroon MF

    更新日期：2014-12-13 00:00:00

  • Assessment of automated analyses of cell migration on flat and nanostructured surfaces.

    abstract：:Motility studies of cells often rely on computer software that analyzes time-lapse recorded movies and establishes cell trajectories fully automatically. This raises the question of reproducibility of results, since different programs could yield significantly different results of such automated analysis. The fact tha...

    journal_title：Computational and structural biotechnology journal

    pub_type： 杂志文章

    doi：10.5936/csbj.201207004

    authors： Grădinaru C,Lopacińska JM,Huth J,Kestler HA,Flyvbjerg H,Mølhave K

    更新日期：2012-11-21 00:00:00

  • Predicting the impacts of mutations on protein-ligand binding affinity based on molecular dynamics simulations and machine learning methods.

    abstract：Purpose:Mutation-induced variation of protein-ligand binding affinity is the key to many genetic diseases and the emergence of drug resistance, and therefore predicting such mutation impacts is of great importance. In this work, we aim to predict the mutation impacts on protein-ligand binding affinity using efficient s...

    journal_title：Computational and structural biotechnology journal

    pub_type： 杂志文章

    doi：10.1016/j.csbj.2020.02.007

    authors： Wang DD,Ou-Yang L,Xie H,Zhu M,Yan H

    更新日期：2020-02-20 00:00:00

  • Characterization of ENU-induced Mutations in Red Blood Cell Structural Proteins.

    abstract：:Murine models with modified gene function as a result of N-ethyl-N-nitrosourea (ENU) mutagenesis have been used to study phenotypes resulting from genetic change. This study investigated genetic factors associated with red blood cell (RBC) physiology and structural integrity that may impact on blood component storage ...

    journal_title：Computational and structural biotechnology journal

    pub_type： 杂志文章

    doi：10.5936/csbj.201303012

    authors： Kildey K,Flower RL,Tran TV,Tunningley R,Harris J,Dean MM

    更新日期：2013-09-23 00:00:00

  • Fungi.guru: Comparative genomic and transcriptomic resource for the fungi kingdom.

    abstract：:The fungi kingdom is composed of eukaryotic heterotrophs, which are responsible for balancing the ecosystem and play a major role as decomposers. They also produce a vast diversity of secondary metabolites, which have antibiotic or pharmacological properties. However, our lack of knowledge of gene function in fungi pr...

    journal_title：Computational and structural biotechnology journal

    pub_type： 杂志文章

    doi：10.1016/j.csbj.2020.11.019

    authors： Lim JJJ,Koh J,Moo JR,Villanueva EMF,Putri DA,Lim YS,Seetoh WS,Mulupuri S,Ng JWZ,Nguyen NLU,Reji R,Foo H,Zhao MX,Chan TL,Rodrigues EE,Kairon RS,Hee KM,Chee NC,Low AD,Chen ZHX,Lim SC,Lunardi V,Fong TC,Chua CX

    更新日期：2020-11-20 00:00:00

  • A Review on Genomics APIs.

    abstract：:The constant improvement and falling prices of whole human genome Next Generation Sequencing (NGS) has resulted in rapid adoption of genomic information at both clinics and research institutions. Considered together, the complexity of genomics data, due to its large volume and diversity along with the need for genomic...

    journal_title：Computational and structural biotechnology journal

    pub_type： 杂志文章,评审

    doi：10.1016/j.csbj.2015.10.004

    authors： Swaminathan R,Huang Y,Moosavinasab S,Buckley R,Bartlett CW,Lin SM

    更新日期：2015-10-31 00:00:00

  • Prediction of Ligand Transport along Hydrophobic Enzyme Nanochannels.

    abstract：:Buried active sites of enzymes are connected to the bulk solvent through a network of hydrophobic channels. We developed a discretized model that can accurately predict ligand transport along hydrophobic channels up to six orders of magnitude faster than any other existing method. The non-dimensional nature of the mod...

    journal_title：Computational and structural biotechnology journal

    pub_type： 杂志文章

    doi：10.1016/j.csbj.2019.06.001

    authors： Escalante DE,Aksan A

    更新日期：2019-06-11 00:00:00

  • Allosteric inhibition explained through conformational ensembles sampling distinct "mixed" states.

    abstract：:Allosteric modulation provides an effective avenue for selective and potent enzyme inhibition. Here, we summarize and critically discuss recent advances on the mechanisms of allosteric partial agonists for three representative signalling enzymes activated by cyclic nucleotides: the cAMP-dependent protein kinase (PKA),...

    journal_title：Computational and structural biotechnology journal

    pub_type： 杂志文章,评审

    doi：10.1016/j.csbj.2020.10.026

    authors： Byun JA,VanSchouwen B,Akimoto M,Melacini G

    更新日期：2020-11-11 00:00:00

  • Ancestral zinc-finger bearing protein MucR in alpha-proteobacteria: A novel xenogeneic silencer?

    abstract：:The MucR/Ros family protein is conserved in alpha-proteobacteria and characterized by its zinc-finger motif that has been proposed as the ancestral domain from which the eukaryotic C2H2 zinc-finger structure evolved. In the past decades, accumulated evidences have revealed MucR as a pleiotropic transcriptional regulat...

    journal_title：Computational and structural biotechnology journal

    pub_type： 杂志文章,评审

    doi：10.1016/j.csbj.2020.11.028

    authors： Jiao J,Tian CF

    更新日期：2020-11-19 00:00:00

  • ASJA: A Program for Assembling Splice Junctions Analysis.

    abstract：:RNA splicing may generate different kinds of splice junctions, such as linear, back-splice and fusion junctions. Only a limited number of programs are available for detection and quantification of splice junctions. Here, we present Assembling Splice Junctions Analysis (ASJA), a software package that identifies and cha...

    journal_title：Computational and structural biotechnology journal

    pub_type： 杂志文章

    doi：10.1016/j.csbj.2019.08.001

    authors： Zhao J,Li Q,Li Y,He X,Zheng Q,Huang S

    更新日期：2019-08-07 00:00:00

  • Rewired functional regulatory networks among miRNA isoforms (isomiRs) from let-7 and miR-10 gene families in cancer.

    abstract：:Classical microRNA (miRNA) has been so far believed as a single sequence, but it indeed contains multiple miRNA isoforms (isomiR) with various sequences and expression patterns. It is not clear whether these diverse isomiRs have potential relationships and whether they contribute to miRNA:mRNA interactions. Here, we a...

    journal_title：Computational and structural biotechnology journal

    pub_type： 杂志文章

    doi：10.1016/j.csbj.2020.05.001

    authors： Liang T,Han L,Guo L

    更新日期：2020-05-13 00:00:00

  • Deep learning predicts microbial interactions from self-organized spatiotemporal patterns.

    abstract：:Microbial communities organize into spatial patterns that are largely governed by interspecies interactions. This phenomenon is an important metric for understanding community functional dynamics, yet the use of spatial patterns for predicting microbial interactions is currently lacking. Here we propose supervised dee...

    journal_title：Computational and structural biotechnology journal

    pub_type： 杂志文章

    doi：10.1016/j.csbj.2020.05.023

    authors： Lee JY,Sadler NC,Egbert RG,Anderton CR,Hofmockel KS,Jansson JK,Song HS

    更新日期：2020-05-29 00:00:00

  • Identification and characterisation of putative drug binding sites in human ATP-binding cassette B5 (ABCB5) transporter.

    abstract：:The human ATP-binding cassette B5 (ABCB5) transporter, a member of the ABC transporter superfamily, is linked to chemoresistance in tumour cells by drug effluxion. However, little is known about its structure and drug-binding sites. In this study, we generated an atomistic model of the full-length human ABCB5 transpor...

    journal_title：Computational and structural biotechnology journal

    pub_type： 杂志文章

    doi：10.1016/j.csbj.2020.12.042

    authors： Tangella LP,Arooj M,Deplazes E,Gray ES,Mancera RL

    更新日期：2020-12-30 00:00:00

  • Multivariate linear QSPR/QSAR models: Rigorous evaluation of variable selection for PLS.

    abstract：:Basic chemometric methods for making empirical regression models for QSPR/QSAR are briefly described from a user's point of view. Emphasis is given to PLS regression, simple variable selection and a careful and cautious evaluation of the performance of PLS models by repeated double cross validation (rdCV). A demonstra...

    journal_title：Computational and structural biotechnology journal

    pub_type： 杂志文章,评审

    doi：10.5936/csbj.201302007

    authors： Varmuza K,Filzmoser P,Dehmer M

    更新日期：2013-03-02 00:00:00

  • A guide to the identification of metabolites in NMR-based metabonomics/metabolomics experiments.

    abstract：:Metabonomics/metabolomics is an important science for the understanding of biological systems and the prediction of their behaviour, through the profiling of metabolites. Two technologies are routinely used in order to analyse metabolite profiles in biological fluids: nuclear magnetic resonance (NMR) spectroscopy and ...

    journal_title：Computational and structural biotechnology journal

    pub_type： 杂志文章

    doi：10.1016/j.csbj.2016.02.005

    authors： Dona AC,Kyriakides M,Scott F,Shephard EA,Varshavi D,Veselkov K,Everett JR

    更新日期：2016-03-09 00:00:00

  • Homology modeling in the time of collective and artificial intelligence.

    abstract：:Homology modeling is a method for building protein 3D structures using protein primary sequence and utilizing prior knowledge gained from structural similarities with other proteins. The homology modeling process is done in sequential steps where sequence/structure alignment is optimized, then a backbone is built and ...

    journal_title：Computational and structural biotechnology journal

    pub_type： 杂志文章,评审

    doi：10.1016/j.csbj.2020.11.007

    authors： Hameduh T,Haddad Y,Adam V,Heger Z

    更新日期：2020-11-14 00:00:00

  • Microvesicles from indoxyl sulfate-treated endothelial cells induce vascular calcification in vitro.

    abstract：:Vascular calcification (VC), an unpredictable pathophysiological process and critical event in patients with cardiovascular diseases (CVDs), is the leading cause of morbi-mortality and disability in chronic kidney disease (CKD) patients worldwide. Currently, no diagnostic method is available for identifying patients a...

    journal_title：Computational and structural biotechnology journal

    pub_type： 杂志文章

    doi：10.1016/j.csbj.2020.04.006

    authors： Alique M,Bodega G,Corchete E,García-Menéndez E,de Sequera P,Luque R,Rodríguez-Padrón D,Marqués M,Portolés J,Carracedo J,Ramírez R

    更新日期：2020-04-09 00:00:00