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81.
Asker Y. Khapchaev D. Martin Watterson Vladimir P. Shirinsky 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2021,1868(11):119104
BackgroundMyosin light chain kinase (MLCK) is a Ca2+-calmodulin-dependent enzyme dedicated to phosphorylate and activate myosin II to provide force for various motile processes. In smooth muscle cells and many other cells, small MLCK (S-MLCK) is a major isoform. S-MLCK is an actomyosin-binding protein firmly attached to contractile machinery in smooth muscle cells. Still, it can leave this location and contribute to other cellular processes. However, molecular mechanisms for switching the S-MLCK subcellular localization have not been described.MethodsSite-directed mutagenesis and in vitro protein phosphorylation were used to study functional roles of discrete in-vivo phosphorylated residues within the S-MLCK actin-binding domain. In vitro co-sedimentation analysis was applied to study the interaction of recombinant S-MLCK actin-binding fragment with filamentous actin. Subcellular distribution of phosphomimicking S-MLCK mutants was studied by fluorescent microscopy and differential cell extraction.ResultsPhosphorylation of S-MLCK actin-binding domain at Ser25 and/or Thr56 by proline-directed protein kinases or phosphomimicking these posttranslational modifications alters S-MLCK binding to actin filaments both in vitro and in cells, and induces S-MLCK subcellular translocation with no effect on the enzyme catalytic properties.ConclusionsPhosphorylation of the amino terminal actin-binding domain of S-MLCK renders differential subcellular targeting of the enzyme and may, thereby, contribute to a variety of context-dependent responses of S-MLCK to cellular and tissue stimuli.General significanceS-MLCK physiological function can potentially be modulated via phosphorylation of its actin recognition domain, a regulation distinct from the catalytic and calmodulin regulatory domains. 相似文献
82.
Milosavljevic Isidora Jakovljevic Vladimir Petrovic Dejan Draginic Nevena Jeremic Jovana Mitrovic Miroslav Zivkovic Vladimir Srejovic Ivan Stojic Vladislava Bolevich Sergey Andjelkovic Nebojsa 《Molecular and cellular biochemistry》2021,476(11):4167-4175
Molecular and Cellular Biochemistry - The aim of our study was to investigate the effects of one-month consumption of polyphenol-rich standardized Aronia melanocarpa extract (SAE) on redox status... 相似文献
83.
Montana Vedrana Flint Daniel Waagepetersen Helle S. Schousboe Arne Parpura Vladimir 《Neurochemical research》2021,46(10):2551-2579
Neurochemical Research - Astrocytes have a prominent role in metabolic homeostasis of the brain and can signal to adjacent neurons by releasing glutamate via a process of regulated exocytosis.... 相似文献
84.
Sukhorukov Vladimir S. Mudzhiri Natalia M. Voronkova Anastasia S. Baranich Tatiana I. Glinkina Valeria V. Illarioshkin Sergey N. 《Biochemistry. Biokhimii?a》2021,86(6):667-679
Biochemistry (Moscow) - Alzheimer’s disease is the most common age-related neurodegenerative disease. Understanding of its etiology and pathogenesis is constantly expanding. Thus, the... 相似文献
85.
Shilovsky Gregory A. Putyatina Tatyana S. Morgunova Galina V. Seliverstov Alexander V. Ashapkin Vasily V. Sorokina Elena V. Markov Alexander V. Skulachev Vladimir P. 《Biochemistry. Biokhimii?a》2021,86(4):433-448
Biochemistry (Moscow) - This review discusses genetic and molecular pathways that link circadian timing with metabolism, resulting in the emergence of positive and negative regulatory feedback... 相似文献
86.
Valentin M. Tabakmakher Andrei M. Gigolaev Steve Peigneur Nikolay A. Krylov Jan Tytgat Anton O. Chugunov Alexander A. Vassilevski Roman G. Efremov 《Biophysical journal》2021,120(12):2471-2481
The α-Hairpinins are a family of plant defense peptides with a common fold presenting two short α-helices stabilized by two invariant S–S-bridges. We have shown previously that substitution of just two amino acid residues in a wheat α-hairpinin Tk-AMP-X2 leads to Tk-hefu-2 that features specific affinity to voltage-gated potassium channels KV1.3. Here, we utilize a combined molecular modeling approach based on molecular dynamics simulations and protein surface topography technique to improve the affinity of Tk-hefu-2 to KV1.3 while preserving its specificity. An important advance of this work compared with our previous studies is transition from the analysis of various physicochemical properties of an isolated toxin molecule to its consideration in complex with its target, a membrane-bound ion channel. As a result, a panel of computationally designed Tk-hefu-2 derivatives was synthesized and tested against KV1.3. The most active mutant Tk-hefu-10 showed a half-maximal inhibitory concentration of ~150 nM being >10 times more active than Tk-hefu-2 and >200 times more active than the original Tk-hefu. We conclude that α-hairpinins provide an attractive disulfide-stabilized scaffold for the rational design of ion channel inhibitors. Furthermore, the success rate can be considerably increased by the proposed “target-based” iterative strategy of molecular design. 相似文献
87.
88.
Damer P. Blake Vladimir Vrba Dong Xia Isa Danladi Jatau Simon Spiro Matthew J. Nolan Greg Underwood Fiona M. Tomley 《International journal for parasitology》2021,51(8):621-634
More than 68 billion chickens were produced globally in 2018, emphasising their major contribution to the production of protein for human consumption and the importance of their pathogens. Protozoan Eimeria spp. are the most economically significant parasites of chickens, incurring global costs of more than UK £10.4 billion per annum. Seven Eimeria spp. have long been recognised to infect chickens, with three additional cryptic operational taxonomic units (OTUs) first described more than 10 years ago. As the world’s farmers attempt to reduce reliance on routine use of antimicrobials in livestock production, replacing drugs that target a wide range of microbes with precise species- and sometimes strain-specific vaccines, the breakthrough of cryptic genetic types can pose serious problems. Consideration of biological characteristics including oocyst morphology, pathology caused during infection and pre-patent periods, combined with gene-coding sequences predicted from draft genome sequence assemblies, suggest that all three of these cryptic Eimeria OTUs possess sufficient genetic and biological diversity to be considered as new and distinct species. The ability of these OTUs to compromise chicken bodyweight gain and escape immunity induced by current commercially available anticoccidial vaccines indicates that they could pose a notable threat to chicken health, welfare, and productivity. We suggest the names Eimeria lata n. sp., Eimeria nagambie n. sp. and Eimeria zaria n. sp. for OTUs x, y and z, respectively, reflecting their appearance (x) or the origins of the first isolates of these novel species (y, z). 相似文献
89.
Tabakmakher V. M. Kuzmenkov A. I. Gigolaev A. M. Pinheiro-Junior E. L. Peigneur S. Efremov R. G. Tytgat J. Vassilevski A. A. 《Journal of Evolutionary Biochemistry and Physiology》2021,57(2):386-403
Journal of Evolutionary Biochemistry and Physiology - In mammals, about 40 isoforms of voltage-gated potassium channels (KVs) have been found. To study such a variety of KVs, substances are needed... 相似文献
90.
Demin Konstantin A. Refeld Aleksandr G. Bogdanova Anna A. Prazdnova Evgenya V. Popov Igor V. Kutsevalova Olga Yu. Ermakov Alexey M. Bren Anzhelica B. Rudoy Dmitry V. Chistyakov Vladimir A. Weeks Richard Chikindas Michael L. 《Probiotics and antimicrobial proteins》2021,13(4):926-948
Probiotics and Antimicrobial Proteins - Pathogenic Candida and infections caused by those species are now considered as a serious threat to public health. The treatment of candidiasis is... 相似文献