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991.
Cellular functions of an organism are maintained by protein-protein interactions. Those proteins that bind multiple partners asynchronously (date hub proteins) are important to make the interaction network coordinated. It is known that many date hub proteins bind different partners at overlapping (OV) interfaces. To understand how OV interfaces of date hub proteins can recognize multiple partners, we analyzed the difference between OV and non-overlapping (Non-OV) regions of interfaces involved in the binding of different partners. By using the structures of 16 date hub proteins with various interaction partners (ranging from 5 to 33), we compared buried surface area, compositions of amino acid residues and secondary structures, and side-chain orientations. It was found that buried interface residues are important for recognizing multiple partners, while exposed interface residues are important for determining specificity to a particular ligand. In addition, our analyses reveal that residue compositions in OV and Non-OV regions are different and that residues in OV region show diverse side-chain torsion angles to accommodate binding to multiple targets. 相似文献
992.
The SMK box (SAM-III) translational riboswitches were identified in S-adenosyl-l-methionine (SAM) synthetase metK genes in members of Lactobacillales. This riboswitch switches between two alternative conformations in response to intracellular SAM concentration and controls metK expression at the level of translation initiation. We previously reported the crystal structure of the SAM-bound SMK box riboswitch. In this study, we combined selective 2′-hydroxyl acylation analyzed by primer extension chemical probing with mutagenesis to probe the ligand-induced conformational switching mechanism. We revealed that while the majority of the apo SMK box RNA molecules exist in an alternatively base-paired (ON) conformation, a subset of them pre-organize into a SAM-bound-like (READY) conformation, which, upon SAM exposure, is selectively stabilized into the SAM-bound (OFF) conformation through an induced-fit mechanism. Mutagenesis showed that the ON state is only slightly more stable than the READY state, as several single-nucleotide substitutions in a hypervariable region outside the SAM-binding core can alter the folding landscape to favor the READY state. Such SMK variants display a “constitutively OFF” behavior both in vitro and in vivo. Time-resolved and temperature-dependent selective 2′-hydroxyl acylation analyzed by primer extension analyses revealed adaptation of the SMK box RNA to its mesothermal working environment. The latter analysis revealed that the SAM-bound SMK box RNA follows a two-step folding/unfolding process. 相似文献
993.
994.
Background
Distamycin A is a prototype minor groove binder, which binds to B-form DNA, preferentially at A/T rich sites. Extensive work in the past few decades has characterized the binding at the level of double stranded DNA. However, effect of the same on physiological DNA, i.e. DNA complexed in chromatin, has not been well studied. Here we elucidate from a structural perspective, the interaction of distamycin with soluble chromatin, isolated from Sprague-Dawley rat.Methodology/Principal Findings
Chromatin is a hierarchical assemblage of DNA and protein. Therefore, in order to characterize the interaction of the same with distamycin, we have classified the system into various levels, according to the requirements of the method adopted, and the information to be obtained. Isothermal titration calorimetry has been employed to characterize the binding at the levels of chromatin, chromatosome and chromosomal DNA. Thermodynamic parameters obtained thereof, identify enthalpy as the driving force for the association, with comparable binding affinity and free energy for chromatin and chromosomal DNA. Reaction enthalpies at different temperatures were utilized to evaluate the change in specific heat capacity (ΔCp), which, in turn, indicated a possible binding associated structural change. Ligand induced structural alterations have been monitored by two complementary methods - dynamic light scattering, and transmission electron microscopy. They indicate compaction of chromatin. Using transmission electron microscopy, we have visualized the effect of distamycin upon chromatin architecture at di- and trinucleosome levels. Our results elucidate the simultaneous involvement of linker bending and internucleosomal angle contraction in compaction process induced by distamycin.Conclusions/Significance
We summarize here, for the first time, the thermodynamic parameters for the interaction of distamycin with soluble chromatin, and elucidate its effect on chromatin architecture. The study provides insight into a ligand induced compaction phenomenon, and suggests new mechanisms of chromatin architectural alteration. 相似文献995.
Background
Neuroinflammation associated with Japanese encephalitis (JE) is mainly due to the activation of glial cells with subsequent release of proinflammatory mediators from them. The recognition of viral RNA, in part, by the pattern recognition receptor retinoic acid-inducible gene I (RIG-I) has been indicated to have a role in such processes. Even though neurons are also known to express this receptor, its role after JE virus (JEV) infections is yet to be elucidated.Methodology/Principal Findings
Upon infecting murine neuroblastoma cells and primary cortical neurons with JEV the expression profile of key proinflammatory cyto/chemokines were analyzed by qRT-PCR and bead array, both before and after ablation of RIG-I. Immunoblotting was performed to evaluate the levels of key molecules downstream to RIG-I leading to production of proinflammatory mediators. Changes in the intracellular viral antigen expression were confirmed by intracellular staining and immunoblotting. JEV infection induced neuronal expression of IL-6, IL-12p70, MCP-1, IP-10 and TNF-α in a time-dependent manner, which showed significant reduction upon RIG-I ablation. Molecules downstream to RIG-I showed significant changes upon JEV-infection, that were modulated following RIG-I ablation. Ablation of RIG-I in neurons also increased their susceptibility to JEV.Conclusions/Significance
In this study we propose that neurons are one of the potential sources of proinflammatory cyto/chemokines in JEV-infected brain that are produced via RIG-I dependent pathways. Ablation of RIG-I in neurons leads to increased viral load and reduced release of the cyto/chemokines. 相似文献996.
Shalini Dhyani Debbie Bartlett Rakesh Kadaverugu Rajarshi Dasgupta Paras Pujari Parikshit Verma 《Restoration Ecology》2020,28(5):1026-1031
Sustainable land restoration is the key to restore degraded land, halt biodiversity loss, and reinstate ecosystem services for human well‐being. Restoration needs to be planned and conducted with due recognition to growing climate uncertainty with an evolved understanding of the future restoration targets. The present opinion article attempts to provide an overview on an integrated climate sensitive restoration framework that recognizes the local participation in mapping degraded lands, identification of species for supporting species modeling to better understand climate uncertainty. Involvement of citizen science‐based restoration monitoring tools can contribute to big data analytics for ecological monitoring and policy support. The Framework potentially helps in sustainable land restoration by transformative changes for achieving the UN Decade on Ecosystem Restoration (2021–2030), Sustainable Development Goals 15, and addressing the post‐2020 Global Biodiversity Framework. However, to realize success, climate finance mechanisms to drive restoration should be seriously considered for reducing bias and enhancing opportunities of equitable sharing in the era of corruption, authoritarianism, and regulatory capture. 相似文献
997.
Background
Three new analogs of berberine with aryl/arylalkyl amino carbonyl methyl substituent at the 9-position of the isoquinoline chromophore along with berberrubine were studied for their binding to tRNAphe by wide variety of biophysical techniques like spectrophotometry, spectrofluorimetry, circular dichroism, thermal melting, viscosity and isothermal titration calorimetry.Methodology/Principal Findings
Scatchard binding isotherms revealed that the cooperative binding mode of berberine was propagated in the analogs also. Thermal melting studies showed that all the 9-O-N-aryl/arylalkyl amino carbonyl methyl substituted berberine analogs stabilized the tRNAphe more in comparison to berberine. Circular dichroism studies showed that these analogs perturbed the structure of tRNAphe more in comparison to berberine. Ferrocyanide quenching studies and viscosity results proved the intercalative binding mode of these analogs into the helical organization of tRNAphe. The binding was entropy driven for the analogs in sharp contrast to the enthalpy driven binding of berberine. The introduction of the aryl/arylalkyl amino carbonyl methyl substituent at the 9-position thus switched the enthalpy driven binding of berberine to entropy dominated binding. Salt and temperature dependent calorimetric studies established the involvement of multiple weak noncovalent interactions in the binding process.Conclusions/Significance
The results showed that 9-O-N-aryl/arylalkyl amino carbonyl methyl substituted berberine analogs exhibited almost ten folds higher binding affinity to tRNAphe compared to berberine whereas the binding of berberrubine was dramatically reduced by about twenty fold in comparison to berberine. The spacer length of the substitution at the 9-position of the isoquinoline chromophore appears to be critical in modulating the binding affinities towards tRNAphe. 相似文献998.
Study on geometric properties of nanoparticles and their relation with biomolecular activities, especially protein is quite a new field to explore. This work was carried out towards this direction where images of gold nanoparticles obtained from transmission electron microscopy were processed to extract their size and area profile at different experimental conditions including and excluding a protein, citrate synthase. Since the images were ill-posed, texture of a context-window for each pixel was used as input to a back-propagation network architecture to obtain decision on its membership as nanoparticle. The segmented images were further analysed by k-means clustering to derive geometric properties of individual nanoparticles even from their assembled form. The extracted geometric information was found to be crucial to give a model featuring porous cage like configuration of nanoparticle assembly using which the chaperone like activity of gold nanoparticles can be explained. 相似文献
999.
Background
Cytochrome P450 monooxygenases form a large superfamily of enzymes that catalyze diverse reactions. The P450 SU1 gene from the soil bacteria Streptomyces griseolus encodes CYP105A1 which acts on various substrates including sulfonylurea herbicides, vitamin D, coumarins, and based on the work presented here, brassinosteroids. P450 SU1 is used as a negative-selection marker in plants because CYP105A1 converts the relatively benign sulfonyl urea pro-herbicide R7402 into a highly phytotoxic product. Consistent with its use for negative selection, transgenic Arabidopsis plants were generated with P450 SU1 situated between recognition sequences for FLP recombinase from yeast to select for recombinase-mediated excision. However, unexpected and prominent developmental aberrations resembling those described for mutants defective in brassinosteroid signaling were observed in many of the lines. 相似文献1000.
Soumitra Maiti Jolly Basak Sabyasachi Kundagrami Anirban Kundu Amita Pal 《Molecular biotechnology》2011,47(2):95-104
Mungbean Yellow Mosaic India Virus (MYMIV) belonging to the genus begomovirus causes the yellow mosaic disease in a number
of economically important edible grain legumes including mungbean (Vigna radiata), urdbean (Vigna mungo) and soybean (Glycine max). The disease is severe, critical, open spread and inflicts heavy yield losses annually. The objective of this study is to
develop molecular markers linked to MYMIV-resistance to facilitate genotyping of urdbean and mungbean germplasms for MYMIV-reaction.
Resistance-linked molecular markers were successfully developed from consensus motifs of other resistance (R) gene or R gene
homologue sequences. Applying linked marker-assisted genotyping, plant breeders can carry out repeated genotyping throughout
the growing season in absence of any disease incidence. Two MYMIV-resistance marker loci, YR4 and CYR1, were identified and
of these two CYR1 is completely linked with MYMIV-resistant germplasms and co-segregating with MYMIV-resistant F2, F3 progenies of urdbean. The present study demonstrated that these two markers could be efficiently employed together in a multiplex-PCR-reaction
for genotyping both V. mungo and V. radiata germplasms from field grown plants and also directly from the seed stock. This method of genotyping would save time and labour
during the introgression of MYMIV-resistance through molecular breeding, as methods of phenotyping against begomoviruses are
tedious, labour and time intensive. 相似文献