scholarly journals Structural insights into photoactivation of plant Cryptochrome-2

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Malathy Palayam ◽  
Jagadeesan Ganapathy ◽  
Angelica M. Guercio ◽  
Lior Tal ◽  
Samuel L. Deck ◽  
...  
Keyword(s):  
Structural Changes ◽  
Active State ◽  
Light Signaling ◽  
Interacting Proteins ◽  
Structural Elements ◽  
Evolutionarily Conserved ◽  
Critical Residues ◽  
Systematic Structure ◽  
Cryptochrome 2 ◽  
Structural Insights

AbstractCryptochromes (CRYs) are evolutionarily conserved photoreceptors that mediate various light-induced responses in bacteria, plants, and animals. Plant cryptochromes govern a variety of critical growth and developmental processes including seed germination, flowering time and entrainment of the circadian clock. CRY’s photocycle involves reduction of their flavin adenine dinucleotide (FAD)-bound chromophore, which is completely oxidized in the dark and semi to fully reduced in the light signaling-active state. Despite the progress in characterizing cryptochromes, important aspects of their photochemistry, regulation, and light-induced structural changes remain to be addressed. In this study, we determine the crystal structure of the photosensory domain of Arabidopsis CRY2 in a tetrameric active state. Systematic structure-based analyses of photo-activated and inactive plant CRYs elucidate distinct structural elements and critical residues that dynamically partake in photo-induced oligomerization. Our study offers an updated model of CRYs photoactivation mechanism as well as the mode of its regulation by interacting proteins.

scholarly journals Structural Insights into Photoactivation of Plant Cryptochrome-2

2020 ◽  
Author(s):  
Malathy Palayam ◽  
Jagadeesan Ganapathy ◽  
Angelica M. Guercio ◽  
Lior Tal ◽  
Samuel L. Deck ◽  
...  
Keyword(s):  
Structural Changes ◽  
Active State ◽  
Light Signaling ◽  
Interacting Proteins ◽  
Structural Elements ◽  
Evolutionarily Conserved ◽  
Critical Residues ◽  
Systematic Structure ◽  
Cryptochrome 2 ◽  
Structural Insights

AbstractCryptochromes (CRYs) are evolutionarily conserved photoreceptors that mediate various light-induced responses in bacteria, plants, and animals. Plant cryptochromes govern a variety of critical growth and developmental processes including seed germination, flowering time and entrainment of the circadian clock. CRY’s photocycle involves reduction of their flavin adenine dinucleotide (FAD)-bound chromophore, which is completely oxidized in the dark and semi to fully reduced in the light signaling-active state. Despite the significant progress in characterizing cryptochromes, important aspects of their photochemistry, regulation, and light-induced structural changes remain to be addressed. In this study, we determine the crystal structure of the photosensory domain of Arabidopsis CRY2 in a tetrameric active state. Systematic structure-based analyses of photo-activated and inactive plant CRYs elucidate new structural elements and critical residues that dynamically partake in photo-induced oligomerization. Our study offers an updated model of CRYs photoactivation mechanism as well as the mode of its regulation by interacting proteins.

scholarly journals Structural insights into GlcNAc-1-phosphotransferase that directs lysosomal protein transport

2021 ◽  
Author(s):  
Shuo Du ◽  
Guopeng Wang ◽  
Zhiying Zhang ◽  
Chengying Ma ◽  
Ning Gao ◽  
...  
Keyword(s):  
Protein Transport ◽  
Catalytic Domain ◽  
Structural Similarity ◽  
Initial Step ◽  
Functional Requirements ◽  
Lysosomal Storage ◽  
Cryo Electron Microscopy ◽  
Evolutionarily Conserved ◽  
Critical Residues ◽  
Structural Insights

GlcNAc-1-phosphotransferase (GNPT) catalyzes the initial step in the formation of the mannose-6-phosphate tag that labels ~60 lysosomal proteins for transport. Mutations in GNPT cause lysosomal storage disorders such as mucolipidoses. However, the molecular mechanism of GNPT remains unclear. Mammalian GNPTs are α2β2γ2 hexamers in which the core catalytic α- and β-subunits are derived from GNPTAB. Here, we present the cryo-electron microscopy structure of the Drosophila melanogaster GNPTAB homolog (DmGNPTAB). Four conserved regions located far apart in the sequence fold into the catalytic domain, which exhibits structural similarity to that of the UDP-glucose glycoprotein glucosyltransferase (UGGT). Comparison with UGGT revealed a putative donor substrate-binding site, and the functional requirements of critical residues in human GNPTAB were validated using GNPTAB-knockout cells. DmGNPTAB forms an evolutionarily conserved homodimer, and perturbing the dimer interface undermines the maturation and activity of human GNPTAB. These results provide important insights into GNPT function and related diseases.

scholarly journals Binding and Transcriptional Regulation by 14-3-3 (Bmh) Proteins Requires Residues Outside of the Canonical Motif

2013 ◽  
Vol 13 (1) ◽  
pp. 21-30 ◽  
Author(s):  
Pabitra K. Parua ◽  
Elton T. Young
Keyword(s):  
Regulation Of Transcription ◽  
Interacting Proteins ◽  
Regulatory Domain ◽  
Interaction Sites ◽  
Important Interaction ◽  
Proposed Model ◽  
Evolutionarily Conserved ◽  
Regulatory Mutations ◽  
Canonical Motif ◽  
Transcriptional Phenotype

ABSTRACTEvolutionarily conserved 14-3-3 proteins have important functions as dimers in numerous cellular signaling processes, including regulation of transcription. Yeast 14-3-3 proteins, known as Bmh, inhibit a post-DNA binding step in transcription activation by Adr1, a glucose-regulated transcription factor, by binding to its regulatory domain, residues 226 to 240. The domain was originally defined by regulatory mutations,ADR1calleles that alter activator-dependent gene expression. Here, we report thatADR1calleles and other mutations in the regulatory domain impair Bmh binding and abolish Bmh-dependent regulation both directly and indirectly. The indirect effect is caused by mutations that inhibit phosphorylation of Ser230 and thus inhibit Bmh binding, which requires phosphorylated Ser230. However, several mutations inhibit Bmh binding without inhibiting phosphorylation and thus define residues that provide important interaction sites between Adr1 and Bmh. Our proposed model of the Adr1 regulatory domain bound to Bmh suggests that residues Ser238 and Tyr239 could provide cross-dimer contacts to stabilize the complex and that this might explain the failure of a dimerization-deficient Bmh mutant to bind Adr1 and to inhibit its activity. A bioinformatics analysis of Bmh-interacting proteins suggests that residues outside the canonical 14-3-3 motif might be a general property of Bmh target proteins and might help explain the ability of 14-3-3 to distinguish target and nontarget proteins. Bmh binding to the Adr1 regulatory domain, and its failure to bind when mutations are present, explains at a molecular level the transcriptional phenotype ofADR1cmutants.

scholarly journals Novel Computational Method to Define RNA PSRs Explains Influenza A Virus Nucleotide Conservation

2018 ◽  
Author(s):  
Andrey Chursov ◽  
Nathan Fridlyand ◽  
Albert A. Sufianov ◽  
Oleg I. Kiselev ◽  
Irina Baranovskaya ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
H1n1 Influenza ◽  
Computational Method ◽  
Structural Elements ◽  
Rna Structures ◽  
Stem Loop ◽  
Rna Molecules ◽  
Stem Loop Structure ◽  
Evolutionarily Conserved

ABSTRACTRNA molecules often fold into evolutionarily selected functional structures. Yet, the literature offers neither a satisfactory definition for “structured RNA regions”, nor a computational method to accurately identify such regions. Here, we define structured RNA regions based on the premise that both stems and loops in functional RNA structures should be conserved among RNA molecules sharing high sequence homology. In addition, we present a computational approach to identify RNA regions possessing evolutionarily conserved secondary structures, RNA ISRAEU (RNA Identification of Structured Regions As Evolutionary Unchanged). Applying this method to H1N1 influenza mRNAs revealed previously unknown structured RNA regions that are potentially essential for viral replication and/or propagation. Evolutionary conservation of RNA structural elements may explain, in part, why mutations in some nucleotide positions within influenza mRNAs occur significantly more often than in others. We found that mutations occurring in conserved nucleotide positions may be more disruptive for structured RNA regions than single nucleotide polymorphisms in positions that are more prone to changes. Finally, we predicted computationally a previously unknown stem-loop structure and demonstrated that oligonucleotides complementing the stem (but not the loop or unrelated sequences) reduce viral replicationin vitro.These results contribute to understanding influenza A virus evolution and can be applied to rational design of attenuated vaccines and/or drug designs based on disrupting conserved RNA structural elements.AUTHOR SUMMARYRNA structures play key biological roles. However, the literature offers neither a satisfactory definition for “structured RNA regions” nor the computational methodology to identify such regions. We define structured RNA regions based on the premise that functionally relevant RNA structures should be evolutionarily conserved, and devise a computational method to identify RNA regions possessing evolutionarily conserved secondary structural elements. Applying this method to influenza virus mRNAs of pandemic and seasonal H1N1 influenza A virus generated Predicted Structured Regions (PSRs), which were previously unknown. This explains the previously mysterious sequence conservation among evolving influenza strains. Also, we have experimentally supported existence of a computationally predicted stem-loop structure predicted computationally. Our approach may be useful in designing live attenuated influenza vaccines and/or anti-viral drugs based on disrupting necessary conserved RNA structures.

scholarly journals DEVELOPMENT OF THE NEW INTERNATIONAL FINANCIAL ARCHITECTURE AT THE NATIONAL FINANCIAL SYSTEMS LEVEL

2020 ◽  
Author(s):  
Viorica Lopotenco
Keyword(s):  
World Economy ◽  
Structural Changes ◽  
Dynamic Balance ◽  
System Structure ◽  
Structural Elements ◽  
Financial Systems ◽  
Financial Architecture ◽  
International Financial Architecture ◽  
Overall Performance ◽  
Functioning Mechanism

The fundamental purpose of this paper is to analyze the transformations in the international financial architecture and their impact on the national financial system. The analysis of the international financial architecture's functioning mechanism suggests its similarity with the software system structure. It is static in the way the system functionality is decomposed and divided into implementation teams. The efficiency of international financial architecture's functioning depends mainly on how balanced and interconnected its elements are. Thus, according to systems theory, only by overcoming the deformation of the international financial architecture at all its levels, it is possible to increase the financial system's overall performance. In this regard, maintaining a dynamic balance in the development of the international financial architecture as an integral unit of its structural elements and functions is becoming of urgent importance. This aspect of the research allows the creation of an instrumental and methodological basis for forecasting the directions for further developing the international financial architecture in the context of the globalization of the world economy at the national financial systems level. This study concludes that the complex solution of the international financial architecture challenges involves creating the foundations for implementing progressive structural changes in the economy and contributing to sustainable economic development.

scholarly journals Structural Insights into GluK3-kainate Receptor Desensitization and Recovery

2019 ◽  
Author(s):  
Jyoti Kumari ◽  
Rajesh Vinnakota ◽  
Janesh Kumar
Keyword(s):  
Structural Changes ◽  
Mutational Analysis ◽  
Receptor Activation ◽  
Kainate Receptors ◽  
Kainate Receptor ◽  
Amino Terminal ◽  
Binding Domains ◽  
Domain Interactions ◽  
Structural Insights

AbstractGluK3-kainate receptors are atypical members of the iGluR family that reside at both the pre- and postsynapse and play key role in regulation of synaptic transmission. For better understanding of structural changes that underlie receptor recovery from desensitized state, GluK3 receptors were trapped in desensitized and resting/closed states and structures analyzed using single particle cryo-electron microscopy. We show that receptor recovery from desensitization requires major rearrangements of the ligand binding domains (LBD) while the amino terminal (ATD) and transmembrane domains remain virtually unaltered. While, the desensitized GluK3 has domain organization as seen earlier for another kainate receptor-GluK2, antagonist bound GluK3 trapped a partially “recovered” state with only two LBD domains in dimeric arrangement necessary for receptor activation. Using these structures as guide, we show that the N-linked glycans at the interface of GluK3 ATD and LBD likely mediate inter-domain interactions and attune receptor-gating properties. Mutational analysis also identifies putative N-glycan interacting residues. These results provide a molecular framework for understanding gating properties unique to GluK3 and identify role of N-linked glycosylation in their modulation.

scholarly journals Activation Mechanism of Strigolactone Receptors And Its Impact On Ligand Selectivity Between Host And Parasitic Plants

2021 ◽  
Author(s):  
Jiming Chen ◽  
David C Nelson ◽  
Diwakar Shukla
Keyword(s):  
Structural Changes ◽  
High Sensitivity ◽  
Parasitic Plants ◽  
Binding Pocket ◽  
Active State ◽  
Activation Mechanism ◽  
Ligand Selectivity ◽  
Inactive State ◽  
State Population ◽  
Large Conformational Change

Parastic weeds such as Striga have led to significant losses in agricultural productivity worldwide. These weeds use the plant hormone strigolactone as a germination stimulant. Strigolactone signaling involves substrate binding and hydrolysis followed by a large conformational change of the receptor to a "closed" or "active" state that is able to associate with a downstream signaling partner MAX2/D3. The crystal structure of the active and inactive AtD14 receptor have helped in elucidating the structural changes involved in activation. However, the mechanism by which the receptor activates remains unknown. The ligand dependence of AtD14 activation has been disputed by mutagenesis studies showing that enzymatically inactive receptors are able to form a complex with MAX2 proteins. Furthermore, activation differences between strigolactone receptor in Striga, ShHTL7 and textitAtD14 could contribute to the high sensitivity to strigolactones exhibited by parasitic plants. Using molecular dynamics simulations, we demonstrate that both AtD14 and ShHTL7 could adopt an active conformation in absence of ligand. However, the ShHTL7 receptor exhibits higher population in the inactive apo state as compared to the AtD14 receptor. We demonstrate that this difference in inactive state population is caused by sequence differences between their D-loops and its interactions with the catalytic histidine that prevents full binding pocket closure in ShHTL7. These results indicate that hydrolysis of a strigolactone ligand would enhance the active state population by destabilizing the inactive state in ShHTL7 as compared to AtD14. We also show that the mechanism of activation is more concerted in AtD14 than in ShHTL7 and that the main barrier to activation in ShHTL7 is closing of the binding pocket.

scholarly journals Optimization of the structure of insulating composite materials

2019 ◽  
Vol 13 (1) ◽  
pp. 57-62
Author(s):  
Zeljko Kos ◽  
Valerii Vyrovoi ◽  
Volodymyr Sukhanov ◽  
Mykhailo Zavoloka ◽  
Aleksandr Gokhman ◽  
...  
Keyword(s):  
Structural Changes ◽  
Design System ◽  
Building Structure ◽  
Structural Elements ◽  
Structural System ◽  
Self Organized ◽  
Self Development ◽  
Complex Structural ◽  
Self Organizing

The article deals with the interdependent relationship between the properties of a structure and the properties of a material, which sets the task of reducing them, even they are indistinguishable, to a certain integrity. The object of research and analysis in the article is a building structure, which is seen as an open self-organized complex structural system. In the main part, the processes of the formation of structures are considered, as well as the classification of structural elements. The article concludes with structural changes related to the self-support and self-development of the network of active elements, which allow the manifestation of adaptation effects and the design-system to function during the normalized period. The importance of self-organization processes during the development and operation of construction systems allow us to attribute it to a self-organizing system. Thus, the building structure can be represented as an open and complex self-organizing system.

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