共查询到20条相似文献，搜索用时 15 毫秒
1.
Salome Kylarova Katarina Psenakova Petr Herman Veronika Obsilova Tomas Obsil 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(10):2304-2313
Background
Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2), a member of the Ca?2+/calmodulin-dependent kinase (CaMK) family, functions as an upstream activator of CaMKI, CaMKIV and AMP-activated protein kinase. Thus, CaMKK2 is involved in the regulation of several key physiological and pathophysiological processes. Previous studies have suggested that Ca2+/CaM binding may cause unique conformational changes in the CaMKKs compared with other CaMKs. However, the underlying mechanistic details remain unclear.Methods
In this study, hydrogen-deuterium exchange coupled to mass spectrometry, time-resolved fluorescence spectroscopy, small-angle x-ray scattering and chemical cross-linking were used to characterize Ca2+/CaM binding-induced structural changes in CaMKK2.Results
Our data suggest that: (i) the CaMKK2 kinase domain interacts with the autoinhibitory region (AID) through the N-terminal lobe of the kinase domain including the RP insert, a segment important for targeting downstream substrate kinases; (ii) Ca2+/CaM binding affects the structure of several regions surrounding the ATP-binding pocket, including the activation segment; (iii) although the CaMKK2:Ca2+/CaM complex shows high conformational flexibility, most of its molecules are rather compact; and (iv) AID-bound Ca2+/CaM transiently interacts with the CaMKK2 kinase domain.Conclusions
Interactions between the CaMKK2 kinase domain and the AID differ from those of other CaMKs. In the absence of Ca2+/CaM binding the autoinhibitory region inhibits CaMKK2 by both blocking access to the RP insert and by affecting the structure of the ATP-binding pocket.General significance
Our results corroborate the hypothesis that Ca2+/CaM binding causes unique conformational changes in the CaMKKs relative to other CaMKs. 相似文献2.
Vincenzo Maione Francesca Cantini Mirko Severi Lucia Banci 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(9):1980-1987
Background
The CIA2A protein, in complex with CIAO1, has been proposed to be exclusively implicated in the maturation of cytosolic aconitase. However, how the CIA2A-CIAO1 complex generates active aconitase is still unknown and the available structural information has not provided any crucial insights into the molecular function of CIA2A.Methods
In this work we have characterized the Fe/S cluster binding properties of CIA2A and of the CIA2A-CIAO1 complex via NMR, UV???vis absorption and EPR spectroscopies and we have investigated how the Fe/S cluster is transferred to inactive aconitase/IRP1 protein.Results
We found that an heterotrimeric species formed by two molecules of CIA2A and one of CIAO1 can bind one [4Fe-4S] cluster and that residue Cys90 of CIA2A is one of the cluster ligand. The holo trimeric complex is able to transfer the [4Fe-4S] cluster to apo-IRP1 thus generating the active form of aconitase.Conclusions and general significance
These findings, which highlight a functional role for CIA2A-CIAO1 complex in aconitase maturation, raises a broad interest and can have a high impact on the community studying metal trafficking and iron?sulfur protein biogenesis. The present study can provide solid bases for further investigation of the molecular mechanisms involving also other CIA machinery proteins. 相似文献3.
《Hydrobiologia》1995,302(2):177-178
Announcement
Eight International Symposium of the Biology of the Turbellaria 相似文献4.
Editorial Introduction
Letter from the Editor 相似文献5.
Moshe Salai 《Cell and tissue banking》2000,1(2):101-103
Editorial Introduction
Letter from the Editor 相似文献6.
José M. Martín-Alonso Sonia Casta?ón Pablo Alonso Francisco Parra Ricardo Ordás 《Transgenic research》2004,13(1):1-3
Letter to the Editor
Letter to the editor 相似文献7.
Tiina Nieminen Pyry I. Toivanen Nina Rintanen Tommi Heikura Suvi Jauhiainen Kari J. Airenne Kari Alitalo Varpu Marjomäki Seppo Ylä-Herttuala 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014
Background
Vascular endothelial growth factors (VEGFs) are potential therapeutic agents for treatment of ischemic diseases. Their angiogenic effects are mainly mediated through VEGF receptor 2 (VEGFR2).Methods
Receptor binding, signaling, and biological efficacy of several VEGFR2 ligands were compared to determine their characteristics regarding angiogenic activity and vascular permeability.Results
Tested VEGFR2 ligands induced receptor tyrosine phosphorylation with different efficacy depending on their binding affinities. However, the tyrosine phosphorylation pattern and the activation of the major downstream signaling pathways were comparable. The maximal angiogenic effect stimulated by different VEGFR2 ligands was dependent on their ability to bind to co-receptor Neuropilin (Nrp), which was shown to form complexes with VEGFR2. The ability of these VEGFR2 ligands to induce vascular permeability was dependent on their concentration and VEGFR2 affinity, but not on Nrp binding.Conclusions
VEGFR2 activation alone is sufficient for inducing endothelial cell proliferation, formation of tube-like structures and vascular permeability. The level of VEGFR2 activation is dependent on the binding properties of the ligand used. However, closely similar activation pattern of the receptor kinase domain is seen with all VEGFR2 ligands. Nrp binding strengthens the angiogenic potency without increasing vascular permeability.General significance
This study sheds light on how different structurally closely related VEGFR2 ligands bind to and signal via VEGFR2/Nrp complex to induce angiogenesis and vascular permeability. The knowledge of this study could be used for designing VEGFR2/Nrp ligands with improved therapeutic properties. 相似文献8.
Stefanie Nowak Antonella Di Pizio Anat Levit Masha Y. Niv Wolfgang Meyerhof Maik Behrens 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(10):2162-2173
Background
In humans, bitterness perception is mediated by ~25 bitter taste receptors present in the oral cavity. Among these receptors three, TAS2R10, TAS2R14 and TAS2R46, exhibit extraordinary wide agonist profiles and hence contribute disproportionally high to the perception of bitterness. Perhaps the most broadly tuned receptor is the TAS2R14, which may represent, because of its prominent expression in extraoral tissues, a receptor of particular importance for the physiological actions of bitter compounds beyond taste.Methods
To investigate how the architecture and composition of the TAS2R14 binding pocket enables specific interactions with a complex array of chemically diverse bitter agonists, we carried out homology modeling and ligand docking experiments, subjected the receptor to point-mutagenesis of binding site residues and performed functional calcium mobilization assays.Results
In total, 40 point-mutated receptor constructs were generated to investigate the contribution of 19 positions presumably located in the receptor's binding pocket to activation by 7 different TAS2R14 agonists. All investigated positions exhibited moderate to pronounced agonist selectivity.Conclusions
Since numerous modifications of the TAS2R14 binding pocket resulted in improved responses to individual agonists, we conclude that this bitter taste receptor might represent a suitable template for the engineering of the agonist profile of a chemoreceptive receptor.General significance
The detailed structure-function analysis of the highly promiscuous and widely expressed TAS2R14 suggests that this receptor must be considered as potentially frequent target for known and novel drugs including undesired off-effects. 相似文献9.
《Journal of biological inorganic chemistry》2010,15(5):809-809
SBIC News
A note from the president 相似文献10.
《Journal of biological inorganic chemistry》2010,15(6):987-987
SBIC News
A note from the president 相似文献11.
Mark J. Eisenberg 《Journal of chemical biology》2010,3(2):89-100
JOCB Bulletin
Welcome to the JOCB Bulletin 相似文献12.
Fraser Armstrong 《Journal of biological inorganic chemistry》2007,12(1):138-138
SBIC News
A note from the President 相似文献13.
A. Jerome-Morais S. Bera W. Rachidi P.H. Gann A.M. Diamond 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
Significant data supports the health benefits of selenium although supplementation trials have yielded mixed results. GPx-1, whose levels are responsive to selenium availability, is implicated in cancer etiology by human genetic data. Selenium's ability to alter the phosphorylation of the H2AX, a histone protein that functions in the reduction of DNA damage by recruiting repair proteins to the damage site, following exposure to ionizing radiation and bleomycin was investigated.Methods
Human cell lines that were either exposed to selenium or were transfected with a GPx-1 expression construct were exposed to ionizing radiation or bleomycin. Phosphorylation of histone H2AX was quantified by flow cytometry and survival by the MTT assay. Phosphorylation of the Chk1 and Chk2 checkpoint proteins was quantified by western blotting.Results
In colon-derived cells, selenium increases GPx-1 and attenuated H2AX phosphorylation following genotoxic exposures while the viability of these cells was unaffected. MCF-7 cells and transfectants that express high GPx-1 levels were exposed to ionizing radiation and bleomycin, and H2AX phosphorylation and cell viability were assessed. GPx-1 increased H2AX phosphorylation and viability following the induction of DNA damage while enhancing the levels of activated Chk1 and Chk2.Conclusions
Exposure of mammalian cells to selenium can alter the DNA damage response and do so by mechanisms that are dependent and independent of its effect on GPx-1.General significance
Selenium and GPx-1 may stimulate the repair of genotoxic DNA damage and this may account for some of the benefits attributed to selenium intake and elevated GPx-1 activity. 相似文献14.
15.
John G. Carman Nancy E. Jefferson William F. Campbell 《Plant Cell, Tissue and Organ Culture》1988,12(1):81-81
Erratum
A note from the publishers 相似文献16.
17.
18.
Fraser Armstrong 《Journal of biological inorganic chemistry》2005,10(7):829-829
SBIC News
A note from the President 相似文献19.
José J. G. Moura 《Journal of biological inorganic chemistry》2010,15(8):1355-1355
SBIC News
A note from the President 相似文献20.
Takafumi Kawai Hideki AbeKen-ichi Wakabayashi Yoshitaka Oka 《Biochimica et Biophysica Acta (BBA)/General Subjects》2009,1790(12):1681-1688