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1.
Eukaryotic protein kinases are typically strictly controlled by second messenger binding, protein/protein interactions, dephosphorylations or similar processes. None of these regulatory mechanisms is known to work for protein kinase CK2 (former name “casein kinase 2”), an acidophilic and constitutively active eukaryotic protein kinase. CK2 predominantly exists as a heterotetrameric holoenzyme composed of two catalytic subunits (CK2α) complexed to a dimer of non-catalytic subunits (CK2β). One model of CK2 regulation was proposed several times independently by theoretical docking of the first CK2 holoenzyme structure. According to this model, the CK2 holoenzyme forms autoinhibitory aggregates correlated with trans-autophosphorylation and driven by the down-regulatory affinity between an acidic loop of CK2β and the positively charged substrate binding region of CK2α from a neighboring CK2 heterotetramer. Circular trimeric aggregates in which one-half of the CK2α chains show the predicted inhibitory proximity between those regions were detected within the crystal packing of the human CK2 holoenzyme. Here, we present further in vitro support of the “regulation-by-aggregation” model by an alternative crystal form in which CK2 tetramers are arranged as approximately linear aggregates coinciding essentially with the early predictions. In this assembly, the substrate binding region of every CK2α chain is blocked by a CK2β acidic loop from a neighboring tetramer. We found these crystals with CK2Andante that contains a CK2β variant mutated in a CK2α-contact helix and described to be responsible for a prolonged circadian rhythm in Drosophila. The increased propensity of CK2Andante to form aggregates with completely blocked active sites may contribute to this phenotype.  相似文献   
2.
报道并描述了罂粟科一新变种--重瓣野罂粟(Papaver nudicaule var.pleiopetalum J.C.Shao,var.nov.).该变种与野罂粟的主要区别是具有重瓣花.  相似文献   
3.
报道了2种浙江新记录植物,紫金牛科的软弱杜茎山(Maesa tenera Mez)和茜草科的山东丰花草(Borreria shandongensis F.Z.Li et X.D.Chen.).  相似文献   
4.
Unique species of ceramide (Cer) with very-long-chain polyunsaturated fatty acid (VLCPUFA), mainly 28–32 carbon atoms, 4–5 double bonds, in nonhydroxy and 2-hydroxy forms (n-V Cer and h-V Cer, respectively), are generated in rat spermatozoa from the corresponding sphingomyelins during the acrosomal reaction. The aim of this study was to determine the properties of these sperm-distinctive ceramides in Langmuir monolayers. Individual Cer species were isolated by HPLC and subjected to analysis of surface pressure, surface potential, and Brewster angle microscopy (BAM) as a function of molecular packing. In comparison with known species of Cer, n-V Cer and h-V Cer species showed much larger mean molecular areas and increased molecular dipole moments in liquid expanded phases, which suggest bending and partial hydration of the double bonded portion of the VLCPUFA. The presence of the 2-hydoxyl group induced a closer molecular packing in h-V Cer than in their chain-matched n-V Cer. In addition, all these Cer species showed liquid-expanded to liquid-condensed transitions at room temperature. Existence of domain segregation was confirmed by BAM. Additionally, thermodynamic analysis suggests a phase transition close to the physiological temperature for VLCPUFA-Cers if organized as bulk dispersions.  相似文献   
5.
Novel synthetic mimics of antimicrobial peptides have been developed to exhibit structural properties and antimicrobial activity similar to those of natural antimicrobial peptides (AMPs) of the innate immune system. These molecules have a number of potential advantages over conventional antibiotics, including reduced bacterial resistance, cost-effective preparation, and customizable designs. In this study, we investigate a family of nylon-3 polymer-based antimicrobials. By combining vesicle dye leakage, bacterial permeation, and bactericidal assays with small-angle X-ray scattering (SAXS), we find that these polymers are capable of two interdependent mechanisms of action: permeation of bacterial membranes and binding to intracellular targets such as DNA, with the latter necessarily dependent on the former. We systemically examine polymer-induced membrane deformation modes across a range of lipid compositions that mimic both bacteria and mammalian cell membranes. The results show that the polymers' ability to generate negative Gaussian curvature (NGC), a topological requirement for membrane permeation and cellular entry, in model Escherichia coli membranes correlates with their ability to permeate membranes without complete membrane disruption and kill E. coli cells. Our findings suggest that these polymers operate with a concentration-dependent mechanism of action: at low concentrations permeation and DNA binding occur without membrane disruption, while at high concentrations complete disruption of the membrane occurs. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova.  相似文献   
6.

Background

Hsp90 is a molecular chaperone essential for cell viability in eukaryotes that is associated with the maturation of proteins involved in important cell functions and implicated in the stabilization of the tumor phenotype of various cancers, making this chaperone a notably interesting therapeutic target. Celastrol is a plant-derived pentacyclic triterpenoid compound with potent antioxidant, anti-inflammatory and anticancer activities; however, celastrol's action mode is still elusive.

Results

In this work, we investigated the effect of celastrol on the conformational and functional aspects of Hsp90α. Interestingly, celastrol appeared to target Hsp90α directly as the compound induced the oligomerization of the chaperone via the C-terminal domain as demonstrated by experiments using a deletion mutant. The nature of the oligomers was investigated by biophysical tools demonstrating that a two-fold excess of celastrol induced the formation of a decameric Hsp90α bound throughout the C-terminal domain. When bound, celastrol destabilized the C-terminal domain. Surprisingly, standard chaperone functional investigations demonstrated that neither the in vitro chaperone activity of protecting against aggregation nor the ability to bind a TPR co-chaperone, which binds to the C-terminus of Hsp90α, were affected by celastrol.

Conclusion

Celastrol interferes with specific biological functions of Hsp90α. Our results suggest a model in which celastrol binds directly to the C-terminal domain of Hsp90α causing oligomerization. However, the ability to protect against protein aggregation (supported by our results) and to bind to TPR co-chaperones are not affected by celastrol. Therefore celastrol may act primarily by inducing specific oligomerization that affects some, but not all, of the functions of Hsp90α.

General significance

To the best of our knowledge, this study is the first work to use multiple probes to investigate the effect that celastrol has on the stability and oligomerization of Hsp90α and on the binding of this chaperone to Tom70. This work provides a novel mechanism by which celastrol binds Hsp90α.  相似文献   
7.
The taxonomy of the humpback dolphin genus Sousa has been controversial and unsettled for centuries, but recent work indicates that there are several valid species. A review of multiple lines of evidence from skeletal morphology, external morphology, coloration, molecular genetics, and biogeography, in combination provides strong support for the recognition of four species of Sousa. These include S. teuszii (Kükenthal, 1892), a species with uniform gray coloration and a prominent dorsal hump, which is found in the Atlantic Ocean off West Africa. The species S. plumbea (G. Cuvier, 1829) has similar external appearance to S. teuszii, but has a more pointed dorsal fin. It occurs in the Indian Ocean from South Africa to Myanmar (Burma). The original taxon, S. chinensis (Osbeck, 1765), is reserved for the species that has a larger dorsal fin with no prominent hump, and largely white adult coloration. It ranges from eastern India to central China and throughout Southeast Asia. Finally, we describe a new species of Sousa, the Australian humpback dolphin, which occurs in the waters of the Sahul Shelf from northern Australia to southern New Guinea. It has a lower dorsal fin, more extensive dark color on the body, and a dorsal “cape.” It is separated from the Indo‐Pacific humpback dolphin by a wide distributional gap that coincides with Wallace's Line.  相似文献   
8.
9.
蝙蝠寄生长吸盘属一新种(吸虫纲:枝腺科)   总被引:2,自引:0,他引:2  
本文论述长吸盘属Longitrema一新种——杭州长吸盘吸虫,新种Longilremahangz-houensissp.Nov.,模式标本采自浙江省桐庐县大足鼠耳蝠的小肠中。对新种与近似种梨形长吸盘吸虫Longitremapiriforme(Yamaguti,1939)Chen,1954作了详细的描述。  相似文献   
10.
本文描述采自湖北省恩施和咸宁地区的球蛛科圆腹蛛属一新种-湖北圆腹蛛Dipoena hubeiensis sp.nov.。  相似文献   
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