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1.
Epitope analysis and molecular modeling reveal the topography of the C-terminal peptide of the beta-subunit of human chorionic gonadotropin. 总被引:2,自引:0,他引:2
N Venkatesh S Krishnaswamy S Meuris G S Murthy 《European journal of biochemistry》1999,265(3):1061-1066
Human chorionic gonadotropin (hCG) belongs to a family of heterodimeric glycoprotein hormones that share a common alpha-subunit and a hormone-specific beta-subunit. Among the gonadotropin beta-subunits, greater than 85% homology exists between lutropin (hLH)beta and hCGbeta in their first 114 amino acid residues. However, unlike hLHbeta, hCGbeta contains a 31-amino acid hydrophilic stretch at its carboxyl end (CTPbeta: C-terminal peptide). Although the crystal structure of deglycosylated hCG has been solved, the topography of CTPbeta remains unknown. In this study, we have attempted to define the topology of CTPbeta using mAb probes. We investigated three epitopes on hCGalpha, which are hidden in the hCGalphabeta dimer. However, these epitopes are not hidden in hLH, which has a similar subunit interface to that of hCG, but lacks CTPbeta. This suggested that these epitopes are not masked at the subunit interface of hLH or hCG. Hence, we hypothesized that, in the case of hCG, these epitopes are masked by the CTPbeta. Consistent with this view, several treatments of hCG that removed CTPbeta unmasked these epitopes and enhanced their reactivity with the corresponding mAbs. In order to localise the position of CTPbeta on the alpha-subunit, we used an epitope-mapping strategy [N. Venkatesh & G. S. Murthy (1997) J. Immunol. Methods 202, 173-182] based on differential susceptibility of epitopes to covalent modifications. This enabled us to predict the possible topography of CTPbeta. Further, we were also able to build a model of CTPbeta, completely independently of the epitope-mapping studies, using a homology-based modeling approach [S. Krishnaswamy, I. Lakshminarayanan & S. Bhattacharya (1995) Protein Sci. 4 (Suppl. 2), 86-97]. Results obtained from these two different approaches (epitope analysis and homology modeling) agree with each other and indicate that portions of CTPbeta are in contact with hCGalpha in the native hCG dimer. 相似文献
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S D Kroll J Chen M De Vivo D J Carty A Buku R T Premont R Iyengar 《The Journal of biological chemistry》1992,267(32):23183-23188
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B R Deshpande V L Kallapur K Venkatesh 《Archives internationales de physiologie et de biochimie》1984,92(2):65-72
The quantitative determination of succinic dehydrogenase (SDH), hexokinase (HK), phosphorylase, phosphofructokinase (PFK), glycerol-3-phosphate dehydrogenase (G-3-PDH) and lactate dehydrogenase (LDH) was carried out in the homologous leg muscles of two aquatic Birds. It appears that the leg muscle fibres of the coot, a surface swimmer are more oxidative in nature and appear to utilize glucose as source of energy. The leg muscles of the dabchick, a diving Bird, on the other hand, seem to depend on glycogen as source of energy. The relative activity levels of HK, phosphorylase and PFK support the accepted r?le of glycogen as primary substrate of carbohydrate catabolism in the leg muscles. The ratio of G-3-PDH/LDH in the leg muscles revealed that glycerol 3-phosphate cycle appears to be insufficient to account for the major part of NADH oxidation. However, the LDH activity is quite high in all the muscles. These results led us to believe that glycerol 3-phosphate cycle may function during rest, when the rate of glycolysis will be low. 相似文献
5.
Sebastian Swanson Venkatesh Sivaraman Gevorg Grigoryan Amy E. Keating 《Protein science : a publication of the Protein Society》2022,31(6)
Despite advances in protein engineering, the de novo design of small proteins or peptides that bind to a desired target remains a difficult task. Most computational methods search for binder structures in a library of candidate scaffolds, which can lead to designs with poor target complementarity and low success rates. Instead of choosing from pre‐defined scaffolds, we propose that custom peptide structures can be constructed to complement a target surface. Our method mines tertiary motifs (TERMs) from known structures to identify surface‐complementing fragments or “seeds.” We combine seeds that satisfy geometric overlap criteria to generate peptide backbones and score the backbones to identify the most likely binding structures. We found that TERM‐based seeds can describe known binding structures with high resolution: the vast majority of peptide binders from 486 peptide‐protein complexes can be covered by seeds generated from single‐chain structures. Furthermore, we demonstrate that known peptide structures can be reconstructed with high accuracy from peptide‐covering seeds. As a proof of concept, we used our method to design 100 peptide binders of TRAF6, seven of which were predicted by Rosetta to form higher‐quality interfaces than a native binder. The designed peptides interact with distinct sites on TRAF6, including the native peptide‐binding site. These results demonstrate that known peptide‐binding structures can be constructed from TERMs in single‐chain structures and suggest that TERM information can be applied to efficiently design novel target‐complementing binders. 相似文献
6.
Vishwesh V. Kulkarni Venkatesh Kareenhalli Ganesh A. Viswananthan Marc Riedel 《Systems and synthetic biology》2011,5(3-4):97-104
Genetic regulatory networks respond dynamically to perturbations in the intracellular and extracellular environments of an organism. The GAL system in the yeast Saccharomyces cerevisiae has evolved to utilize galactose as an alternative carbon and energy source, in the absence of glucose in the environment. We present a dynamic model for GAL system in Saccharomyces cerevisiae, which includes a novel mechanism for Gal3p activation upon induction with galactose. The modification enables the model to simulate the experimental observation that in absence of galactose, oversynthesis of Gal3p can also induce the GAL system. We then characterize the memory of the GAL system as the domain of attraction of the steady states. 相似文献
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Rajapurohitam V Kilic A Javadov S Karmazyn M 《Molecular and cellular biochemistry》2012,366(1-2):287-297
We recently identified leptin as a downstream factor mediating the hypertrophic effects of both angiotensin II and endothelin-1 in cardiomyocytes, an effect dependent on increased leptin biosynthesis, however, the mechanism for such increased leptin production is not known. This study was designed to elucidate the mechanisms underlying angiotensin II- and endothelin-1-stimulated synthesis in cultured ventricular myocytes. The hypertrophic effects of both angiotensin II (100 nM) and endothelin-1 (10 nM) were associated with increased leptin secretion and gene expression by 40 and 50 %, and 86 and 68 %, respectively. These effects were associated with significantly increased nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) phosphorylation by 34 and 52 %, as well as enhanced translocation of NF-κB into nuclei and also the NF-κB-DNA binding activity by 35 and 31 % induced by angiotensin II and endothelin-1, respectively. On their own, 24 h treatment with either angiotensin II or endothelin-1 increased cell surface area by 30 and 40 %, protein synthesis by 30 % and the α-skeletal actin gene by 53 and 68 %, respectively, indicating a robust hypertrophic effect whereas this was completely prevented by NF-κB inhibition. In addition, NF-κB inhibition significantly attenuated angiotensin II and endothelin-1-induced p38 MAPK activation whereas inhibition of p38 MAPK blocked both angiotensin II- and endothelin-1-induced increases in leptin secretion. The ability of both angiotensin II- and endothelin-1 to increase leptin production in cardiomyocytes and the resultant hypertrophic response are mediated by NF-κB and dependent on p38 MAPK activation. 相似文献
10.
Mario Pagano J. Dedrick Jordan Susana R. Neves Tracy Nguyen Ravi Iyengar 《Cellular signalling》2008,20(6):1190-1197
The Gs and Gi pathways interact to control the levels of intracellular cAMP. Although coincident signaling through Gs and Gi-coupled receptors can attenuate Gs-stimulated cAMP levels, it is not known if prior activation of the Gi pathway can affect signaling by Gs-coupled receptors. We have found that activated Gαo/i interact with RGS20, a GTPase activating protein for members of the Gαο/i family. Interaction between Gαo/i and RGS20 results in decreased cellular levels of RGS20. This decrease was induced by activated Gαo and Gαi2 but not by Gαq, Gαi1 or Gαi3. The Gαo/i-induced decrease in RGS20 can be blocked by proteasomal inhibitors lactacystin or MG132. Activated Gαo stimulates the ubiquitination of RGS20. The serotonin-1A receptor that couples to Go/i reduces the levels of RGS20 and this effect is blocked by lactacystin, suggesting that Go/i promotes the degradation of RGS20. Expression of RGS20 attenuates the inhibition of β-adrenergic receptor-induced cAMP levels mediated by the serotonin-1A receptor. Prior activation of the serotonin-1A receptor results in loss of the RGS20-mediated attenuation, and the loss of attenuation is blocked when lactacystin is included during the prior treatment. These observations suggest that Go/i-coupled receptors, by stimulating the degradation of RGS20, can regulate how subsequent activation of the Gs and Gi pathways controls cellular cAMP levels, thus allowing for signal integration. 相似文献