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1.
Lukasz Lebioda Marcos H. Hatada A. Tulinsky Irene M. Mavridis 《Journal of molecular biology》1982,162(2):445-458
The 8-fold α/β barrel conformation of 2-keto-3-deoxy-6-phosphogluconate aldolase has been compared to that of triosephosphate isomerase and the A-domain of pyruvate kinase. There are eight supersecondary structure units (α/β) in each of these proteins, and the comparisons were carried out in orientations corresponding to each of the possible congruences, i.e. first to first, first to second,… of the supersecondary structure units. The comparison of the Cα structure of the main chain folding of the three enzymes indicated about 150 equivalences with rootmean-square differences of about 3.1 Å, with no orientational preference, including the aldolase with itself. In addition, there is no sequence homology between the aldolase and the isomerase, and no indication of gene duplication in the former. The lack of orientational preference among the three enzymes suggests convergence to a fold of exceptional stability. However, all three enzymes activate a CH bond adjacent to a carbonyl, and their active sites correspond to the f strand, F helix region of the α/β barrel, thus contradicting the foregoing and suggesting divergent evolution from a common precursor. Other and similar arguments are also presented for and against convergent evolution of these three strikingly similar enzymes. 相似文献
2.
Hilda Mirbaha Dailu Chen Vishruth Mullapudi Sandi Jo Terpack Charles L. White III Lukasz A. Joachimiak Marc I. Diamond 《The Journal of biological chemistry》2022,298(8)
Tau aggregation into ordered assemblies causes neurodegenerative tauopathies. We previously reported that tau monomer exists in either inert (Mi) or seed-competent (Ms) conformational ensembles and that Ms encodes strains, that is, unique, self-replicating, biologically active assemblies. It is unknown if disease begins with Ms formation followed by fibril assembly or if Ms derives from fibrils and is therefore an epiphenomenon. Here, we studied a tauopathy mouse model (PS19) that expresses full-length mutant human (1N4R) tau (P301S). Insoluble tau seeding activity appeared at 2 months of age and insoluble tau protein assemblies by immunoblot at 3 months. Tau monomer from mice aged 1 to 6 weeks, purified using size-exclusion chromatography, contained soluble seeding activity at 4 weeks, before insoluble material or larger assemblies were observed, with assemblies ranging from n = 1 to 3 tau units. By 5 to 6 weeks, large soluble assemblies had formed. This indicated that the first detectable pathological forms of tau were in fact Ms. We next examined posttranslational modifications of tau monomer from 1 to 6 weeks. We detected no phosphorylation unique to Ms in PS19 or human Alzheimer’s disease brains. We conclude that tauopathy begins with formation of the Ms monomer, whose activity is phosphorylation independent. Ms then self assembles to form oligomers before it forms insoluble fibrils. The conversion of tau monomer from Mi to Ms thus constitutes the first detectable step in the initiation of tauopathy in this mouse model, with obvious implications for the origins of tauopathy in humans. 相似文献
3.
Using Meta-BASIC, a highly sensitive method for detection of distant similarity between proteins, we have identified another potential PD-(D/E)XK endonuclease in human herpesvirus 1 (HHV-1) encoded by the UL24 gene. The universal presence of UL24 in completed herpesviral genomes of three major subfamilies, Alphaherpesvirinae, Betaherpesvirinae, and Gammaherpesvirinae, suggests a fundamental role for this predicted PD-(D/E)XK endonuclease activity in the viral life cycle. 相似文献
4.
Hans Lambers Felipe Albornoz Lukasz Kotula Etienne Laliberté Kosala Ranathunge François P. Teste Graham Zemunik 《Plant and Soil》2018,424(1-2):11-33
Background
Mycorrhizal strategies are very effective in enhancing plant acquisition of poorly-mobile nutrients, particularly phosphorus (P) from infertile soil. However, on very old and severely P-impoverished soils, a carboxylate-releasing and P-mobilising cluster-root strategy is more effective at acquiring this growth-limiting resource. Carboxylates are released during a period of only a few days from ephemeral cluster roots. Despite the cluster-root strategy being superior for P acquisition in such environments, these species coexist with a wide range of mycorrhizal species, raising questions about the mechanisms contributing to their coexistence.Scope
We surmise that the coexistence of mycorrhizal and non-mycorrhizal strategies is primarily accounted for by a combination of belowground mechanisms, namely (i) facilitation of P acquisition by mycorrhizal plants from neighbouring cluster-rooted plants, and (ii) interactions between roots, pathogens and mycorrhizal fungi, which enhance the plants’ defence against pathogens. Facilitation of nutrient acquisition by cluster-rooted plants involves carboxylate exudation, making more P available for both themselves and their mycorrhizal neighbours. Belowground nutrient exchanges between carboxylate-exuding plants and mycorrhizal N2-fixing plants appear likely, but require further experimental testing to determine their nutritional and ecological relevance. Anatomical studies of roots of cluster-rooted Proteaceae species show that they do not form a complete suberised exodermis.Conclusions
The absence of an exodermis may well be important to rapidly release carboxylates, but likely lowers root structural defences against pathogens, particularly oomycetes. Conversely, roots of mycorrhizal plants may not be as effective at acquiring P when P availability is very low, but they are better defended against pathogens, and this superior defence likely involves mycorrhizal fungi. Taken together, we are beginning to understand how an exceptionally large number of plant species and P-acquisition strategies coexist on the most severely P-impoverished soils.5.
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PARma is a complete data analysis software for AGO-PAR-CLIP experiments to identify target sites of microRNAs as well as the microRNA binding to these sites. It integrates specific characteristics of the experiments into a generative model. The model and a novel pattern discovery tool are iteratively applied to data to estimate seed activity probabilities, cluster confidence scores and to assign the most probable microRNA. Based on differential PAR-CLIP analysis and comparison to RIP-Chip data, we show that PARma is more accurate than existing approaches. PARma is available from http://www.bio.ifi.lmu.de/PARma 相似文献
8.
Mansouri Borhan Błaszczyk Martyna Binkowski Lukasz J. Sayadi Mohammad Hossein Azadi Nammam Ali Amirabadizadeh Ali Reza Mehrpour Omid 《Biological trace element research》2020,195(1):63-70
Biological Trace Element Research - In low-income and middle-income countries such as Iran, smoking is becoming increasingly popular, especially among young people. This has led to additional... 相似文献
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10.
Edmond M. Linossi Indu R. Chandrashekaran Tatiana B. Kolesnik James M. Murphy Andrew I. Webb Tracy A. Willson Lukasz Kedzierski Alex N. Bullock Jeffrey J. Babon Raymond S. Norton Nicos A. Nicola Sandra E. Nicholson 《PloS one》2013,8(8)
Suppressor of Cytokine Signaling (SOCS)5 is thought to act as a tumour suppressor through negative regulation of JAK/STAT and epidermal growth factor (EGF) signaling. However, the mechanism/s by which SOCS5 acts on these two distinct pathways is unclear. We show for the first time that SOCS5 can interact directly with JAK via a unique, conserved region in its N-terminus, which we have termed the JAK interaction region (JIR). Co-expression of SOCS5 was able to specifically reduce JAK1 and JAK2 (but not JAK3 or TYK2) autophosphorylation and this function required both the conserved JIR and additional sequences within the long SOCS5 N-terminal region. We further demonstrate that SOCS5 can directly inhibit JAK1 kinase activity, although its mechanism of action appears distinct from that of SOCS1 and SOCS3. In addition, we identify phosphoTyr317 in Shc-1 as a high-affinity substrate for the SOCS5-SH2 domain and suggest that SOCS5 may negatively regulate EGF and growth factor-driven Shc-1 signaling by binding to this site. These findings suggest that different domains in SOCS5 contribute to two distinct mechanisms for regulation of cytokine and growth factor signaling. 相似文献