Structure-function relationship
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Serono symposia publications from Raven Press ; Vol. 65
328 s. : obr., tab.
V úvodu je zdůrazněn úzký vztah mezi strukturou a funkcí, současně však i rozdílnost mezi poruchami struktury a funkce, mezi strukturální a funkční patologií: lokální vymezenost strukturál- ních poruch proti holistickému zřetězení funkčních poruch. Z hlediska vývoje je pro organismus rozhodující program, kterým se uplatňuje ve svém prostředí. Program, který se dědičně fixuje, se bezprostředně realizuje funkcí. Té se postupně přizpůsobuje struktura, která funkci umocňuje a také vymezuje, avšak opět je schopná se adaptovat měnící se funkcí (programu).
The close relationship between structure and function is first pointed out. At the same time, however, the difference between changes of structure and of function is stressed: the former is strictly localised, the latter is characterised by chain reactions affecting the entire motor system (holistic). The decisive factor from the developmental point of view is the program which enables the organism to survive. It is this program which is encoded by heredity, and makes adequate functioning possible in the first place. Structure adapts itself only gradually, but then enhances and also lim its function. If necessary, however, structure readapts itself to a change in function (program).
- MeSH
- lidé MeSH
- muskuloskeletální nemoci etiologie rehabilitace MeSH
- muskuloskeletální systém patologie MeSH
- patologie klasifikace MeSH
- pohybové poruchy etiologie rehabilitace MeSH
- rehabilitace trendy MeSH
- svaly patologie MeSH
- vývoj svalů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- srovnávací studie MeSH
The TERT (telomerase reverse transcriptase) subunit of telomerase is an intensively studied macromolecule due to its key importance in maintaining genome integrity and role in cellular aging and cancer. In an effort to provide an up-to-date overview of the topic, we discuss the structure of TERT genes, their alternative splicing products and their functions. Nucleotide databases contain more than 90 full-length cDNA sequences of telomerase protein subunits. Numerous in silico, in vitro and in vivo experimental techniques have revealed a great deal of structural and functional data describing particular features of the telomerase subunit in various model organisms. We explore whether particular findings are generally applicable to telomerases or species-specific. We also discuss in an evolutionary context the role of identified functional TERT subdomains.
- MeSH
- alternativní sestřih MeSH
- eukaryotické buňky enzymologie chemie MeSH
- lidé MeSH
- molekulární evoluce MeSH
- molekulární sekvence - údaje MeSH
- prokaryotické buňky enzymologie chemie MeSH
- telomerasa genetika chemie metabolismus MeSH
- telomery metabolismus MeSH
- vazba proteinů MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
The FOXO subgroup of forkhead transcription factors plays a central role in cell-cycle control, differentiation, metabolism control, stress response and apoptosis. Therefore, the function of these important molecules is tightly controlled by a wide range of protein-protein interactions and posttranslational modifications including phosphorylation, acetylation and ubiquitination. The mechanisms by which these processes regulate FOXO activity are mostly elusive. This review focuses on recent advances in structural studies of forkhead transcription factors and the insights they provide into the mechanism of DNA recognition. On the basis of these data, we discuss structural aspects of protein-protein interactions and posttranslational modifications that target the forkhead domain and the nuclear localization signal of FOXO proteins.
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- acetylace MeSH
- financování organizované MeSH
- forkhead transkripční faktory fyziologie chemie MeSH
- fosforylace MeSH
- konformace proteinů MeSH
- lidé MeSH
- posttranslační úpravy proteinů MeSH
- ubikvitin metabolismus MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- přehledy MeSH
NMDA receptors have received much attention over the last few decades, due to their role in many types of neural plasticity on the one hand, and their involvement in excitotoxicity on the other hand. There is great interest in developing clinically relevant NMDA receptor antagonists that would block excitotoxic NMDA receptor activation, without interfering with NMDA receptor function needed for normal synaptic transmission and plasticity. This review summarizes current understanding of the structure of NMDA receptors and the mechanisms of NMDA receptor activation and modulation, with special attention given to data describing the properties of various types of NMDA receptor inhibition. Our recent analyses point to certain neurosteroids as NMDA receptor inhibitors with desirable properties. Specifically, these compounds show use-dependent but voltage-independent block, that is predicted to preferentially target excessive tonic NMDA receptor activation. Importantly, neurosteroids are also characterized by use-independent unblock, compatible with minimal disruption of normal synaptic transmission. Thus, neurosteroids are a promising class of NMDA receptor modulators that may lead to the development of neuroprotective drugs with optimal therapeutic profiles.
- MeSH
- gating iontového kanálu účinky léků MeSH
- konformace proteinů MeSH
- lidé MeSH
- mozek účinky léků metabolismus MeSH
- nemoci mozku farmakoterapie metabolismus MeSH
- nervový přenos účinky léků MeSH
- neurony účinky léků metabolismus MeSH
- neuroprotektivní látky terapeutické užití MeSH
- receptory N-methyl-D-aspartátu chemie účinky léků metabolismus ultrastruktura MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Sarcoplasmic reticulum (SR) is a specialized tubular network, which not only maintains the intracellular concentration of Ca2+ at a low level but is also known to release and accumulate Ca2+ for the occurrence of cardiac contraction and relaxation, respectively. This subcellular organelle is composed of several phospholipids and different Ca2+-cycling, Ca2+-binding and regulatory proteins, which work in a coordinated manner to determine its function in cardiomyocytes. Some of the major proteins in the cardiac SR membrane include Ca2+-pump ATPase (SERCA2), Ca2+-release protein (ryanodine receptor), calsequestrin (Ca2+-binding protein) and phospholamban (regulatory protein). The phosphorylation of SR Ca2+-cycling proteins by protein kinase A or Ca2+-calmodulin kinase (directly or indirectly) has been demonstrated to augment SR Ca2+-release and Ca2+-uptake activities and promote cardiac contraction and relaxation functions. The activation of phospholipases and proteases as well as changes in different gene expressions under different pathological conditions have been shown to alter the SR composition and produce Ca2+-handling abnormalities in cardiomyocytes for the development of cardiac dysfunction. The post-translational modifications of SR Ca2+ cycling proteins by processes such as oxidation, nitrosylation, glycosylation, lipidation, acetylation, sumoylation, and O GlcNacylation have also been reported to affect the SR Ca2+ release and uptake activities as well as cardiac contractile activity. The SR function in the heart is also influenced in association with changes in cardiac performance by several hormones including thyroid hormones and adiponectin as well as by exercise-training. On the basis of such observations, it is suggested that both Ca2+-cycling and regulatory proteins in the SR membranes are intimately involved in determining the status of cardiac function and are thus excellent targets for drug development for the treatment of heart disease.
Intestinal absorption and biliary excretion of cholesterol represent two major pathways by which the body regulates cholesterol homeostasis. Niemann-Pick C1-like 1 (NPC1L1) is a polytopic transmembrane protein containing a sterol-sensing domain of unknown function. In 2004, NPC1L1 was identified to be essential for intestinal cholesterol absorption, a process that is sensitive to a cholesterol absorption inhibitor ezetimibe. This review summarizes recent studies on NPC1L1 function and proposes a model for NPC1L1-dependent cholesterol uptake. RECENT FINDINGS: Cell culture experiments have shown that NPC1L1 mediates cellular uptake of various sterols but seems to have lower affinity to plant sterols than cholesterol. Transgenic animal studies have demonstrated that hepatic NPC1L1 has the potential to regulate biliary cholesterol excretion. Cholesterol and many transcriptional factors appear to regulate NPC1L1 gene expression. NPC1L1 protein is enriched in the apical membrane of polarized cells and its intracellular itineraries are clearly regulated by cholesterol availability. Evidence suggests cholesterol-regulated clathrin-mediated endocytosis is likely the cellular basis for NPC1L1-dependent cholesterol uptake, which may reconcile disagreement regarding NPC1L1 subcellular localization. SUMMARY: NPC1L1 may have evolved at two sites (apical membrane of enterocytes and canalicular membrane of hepatocytes) to mediate cholesterol uptake through a clathrin-mediated endocytic process, protecting the body against fecal and biliary loss of cholesterol.
- MeSH
- cholesterol sekrece MeSH
- intestinální absorpce MeSH
- játra metabolismus MeSH
- konformace proteinů MeSH
- lidé MeSH
- membránové proteiny fyziologie genetika chemie MeSH
- membránové transportní proteiny fyziologie genetika chemie MeSH
- regulace genové exprese MeSH
- subcelulární frakce metabolismus MeSH
- vztahy mezi strukturou a aktivitou MeSH
- žlučové ústrojí sekrece MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
Although telomerase (EC 2.7.7.49) is important for genome stability and totipotency of plant cells, the principles of its regulation are not well understood. Therefore, we studied subcellular localization and function of the full-length and truncated variants of the catalytic subunit of Arabidopsis thaliana telomerase, AtTERT, in planta. Our results show that multiple sites in AtTERT may serve as nuclear localization signals, as all the studied individual domains of the AtTERT were targeted to the nucleus and/or the nucleolus. Although the introduced genomic or cDNA AtTERT transgenes display expression at transcript and protein levels, they are not able to fully complement the lack of telomerase functions in tert -/- mutants. The failure to reconstitute telomerase function in planta suggests a more complex telomerase regulation in plant cells than would be expected based on results of similar experiments in mammalian model systems.
- MeSH
- Arabidopsis enzymologie genetika MeSH
- buněčné jadérko enzymologie genetika MeSH
- buněčné jádro enzymologie genetika MeSH
- geneticky modifikované rostliny MeSH
- jaderné lokalizační signály genetika MeSH
- katalytická doména genetika MeSH
- listy rostlin genetika MeSH
- proteiny huseníčku genetika metabolismus MeSH
- proteosyntéza MeSH
- regulace genové exprese u rostlin MeSH
- sestřih RNA MeSH
- tabák genetika MeSH
- telomerasa chemie genetika metabolismus MeSH
- terciární struktura proteinů MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
