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991.
Liu Y Fu X Shen J Zhang H Hong W Chang Z 《Biochemical and biophysical research communications》2004,316(3):795-801
Periplasmic proteins of Gram-negative bacteria like Escherichia coli are subjected to immediate affect of environmental fluctuation that may unfold proteins, due to the permeability of the outer membrane to small molecules. They are thus supposedly protected by certain molecular chaperones. Nevertheless, no homologues of typical molecular chaperones have so far been found in periplasm, and the recently reported chaperone activities of periplasmic protein disulfide isomerase (PDI) and peptidyl prolyl isomerase (PPI) seem to be too weak to satisfy such assumed needs. In an attempt to reveal whether periplasmic proteins exhibit certain unusual properties, we discovered that such proteins as a whole are highly resistant to aggregation under a wide variety of denaturing conditions. Furthermore, in an effort to unveil the nature behind this phenomenon we purified and examined four prominent periplasmic proteins. Our results demonstrate that these proteins unfold at rather mild denaturing conditions and expose hydrophobic surfaces during such unfolding process, but hardly form complexes with a typical molecular chaperone. Based on these observations, we propose that the periplasmic proteins have been evolved to resist the formation of aggregates when subjected to various denaturing conditions and molecular chaperones may thus not be needed in periplasm. 相似文献
992.
Integration and channeling of calcium signaling through the CBL calcium sensor/CIPK protein kinase network 总被引:23,自引:0,他引:23
Plant development and reproduction depend on a precise recognition of environmental conditions and the integration of this information with endogenous metabolic and developmental cues. Calcium ions have been firmly established as ubiquitous second messengers functioning in these processes. Calcium signal deciphering and signal-response coupling often involve calcium-binding proteins as responders or relays in this information flow. Here we review the calcineurin B-like protein (CBL) calcium sensor/CBL-interacting protein kinase (CIPK) network as a newly emerging signaling system mediating a complex array of environmental stimuli. We focus particularly on the mechanisms generating signaling specificity. Moreover, we emphasize the functional implications that are emerging from the analyses of CBL and CIPK loss-of-function mutants. 相似文献
993.
Ilaria?Bartalesi Ivano?BertiniEmail author Giulia?Di?Rocco Antonio?Ranieri Antonio?Rosato Murugendra?Vanarotti Paul?R.?Vasos Maria?Silvia?Viezzoli 《Journal of biological inorganic chemistry》2004,9(5):600-608
The minimal mono-heme ferricytochrome
c from Bacillus pasteurii, containing 71 amino acids, has been further investigated through mutagenesis of different positions in the loop containing the iron ligand Met71. These mutations have been designed to sample different aspects of the loop structure, in order to obtain insights into the determinants of the stability of the iron(III) environment. In particular, positions 68, 72 and 75 have been essayed. Gln68 has been mutated to Lys to provide a suitable alternate ligand that can displace Met71 under denaturing conditions. Pro72 has been mutated to Gly and Ala to modify the range of allowed backbone conformations. Ile75, which is in van der Waals contact with Met71 and partly shields a long-lived water molecule in a protein cavity, has been substituted by Val and Ala to affect the network of inter-residue interactions around the metal site. The different contributions of the above amino acids to protein parameters such as structure, redox potential and the overall stability against unfolding with guanidinium hydrochloride are analyzed. While the structure remains essentially the same, the stability decreases with mutations. The comparison with mitochondrial c-type cytochromes is instructive.Abbreviations Bpcytc
soluble fragment of cytochrome c553 from Bacillus pasteurii
- GdmCl
guanidinium chloride
- I75A
Ile75 to Ala mutant
- I75V
Ile75 to Val mutant
- P72A
Pro72 to Ala mutant
- P72G
Pro72 to Gly mutant
- Q68K
Gln75 to Lys mutant
- WT
wild type 相似文献
994.
The role of GRAS proteins in plant signal transduction and development 总被引:32,自引:0,他引:32
GRAS proteins are a recently discovered family of plant-specific proteins named after GAI, RGA and SCR, the first three of its members isolated. Although the Arabidopsis genome encodes at least 33 GRAS protein family members only a few GRAS proteins have been characterized so far. However, it is becoming clear that GRAS proteins exert important roles in very diverse processes such as signal transduction, meristem maintenance and development. Here we present a survey of the different GRAS proteins and review the current knowledge of the function of individual members of this protein family. 相似文献
995.
996.
黑皮质素系统来自阿片-促黑素细胞皮质素原,在中枢摄食行为和能量平衡代谢中起到重要作用,此系统生理功能的发挥主要通过与下丘脑神经元细胞上特定膜受体(黑皮质素受体)结合完成。黑皮质素受体(MCR)有五种亚型(MC1R-MC5R),其中参与体重调节的受体主要是黑皮质素受体3(MC3R)和黑皮质素受体4(MC4R)。MC4R属于G蛋白耦联受体,具有七次跨膜结构。作为一种膜受体,MC4R发挥体重调节作用,一方面受外界激动剂或拮抗剂的调节;另一方面,此受体活化后会影响到细胞内的信号调节通路。研究MC4R的功能首先要了解受体的结构,本文对G蛋白耦联受体的结构进行了较详细的叙述,MC4R经信号调节通路,激活腺苷酸环化酶,增加cAMP的浓度,最终通过影响细胞内基因的转录和翻译,来调节体重和能量的消耗。 相似文献
997.
We previously demonstrated that the substitution of the autolysis loop (residues 143-154 in chymotrypsin numbering) of APC with the corresponding loop of trypsin (APC-Tryp 143-154) has no influence on the proteolytic activity of the protease toward fVa, however, this substitution increases the reactivity of APC with plasma inhibitors so that the mutant exhibits no anticoagulant activity in plasma. To further investigate the role of the autolysis loop in APC and determine whether this loop is a target for modulation by protein S, we evaluated the activity of APC-Tryp 143-154 toward fVa and several plasma inhibitors both in the absence and presence of protein S. Furthermore, we evaluated the active-site topography of APC-Tryp 143-154 by determining the average distance of the closest approach (L) between a fluorescein dye tethered to a tripeptide inhibitor, attached to the active-site of APC-Tryp 143-154, and octadecylrhodamine dyes incorporated into PCPS vesicles both in the absence and presence of protein S. The activity of APC-Tryp 143-154 toward fVa was identical to that of wild-type APC both in the presence and absence of protein S. However, the reactivity of APC-Tryp 143-154 with plasma inhibitors was preferentially improved independent of protein S. The FRET analysis revealed a dramatic change in the active-site topography of APC both in the absence and presence of protein S. Anisotropy measurements revealed that the fluorescein dye has a remarkable degree of rotational freedom in the active-site of APC-Tryp 143-154. These results suggest that the autolysis loop of APC may not be a target for modulation by protein S. This loop, however, plays a critical role in restricting both the specificity and spatial environment of the active-site groove of APC. 相似文献
998.
Chugh J Sharma S Hosur RV 《Protein science : a publication of the Protein Society》2008,17(8):1319-1325
Protein self-association is critical to many biological functions. However, atomic-level structural characterization of these assemblies has remained elusive. In this report we present insights into the mechanistic details of the process of self-association of the 136-residue GTPase effector domain (GED) of the endocytic protein dynamin into a megadalton-sized soluble mass. Our approach is based on NMR monitoring of regulated folding and association through Gdn-HCl titration. The results suggest the evolution of a sequence–self-association paradigm. Equally significantly, the study demonstrates an elegant bottom-up strategy that can render large protein self-assemblies accessible to NMR investigations that have remained difficult to date. 相似文献
999.
Dilated cardiomyopathy (DCM) is a leading cause of heart failure (HF) and cardiac transplantations in Western countries. Single-source gene expression analysis studies have identified potential disease biomarkers and drug targets. However, because of the diversity of experimental settings and relative lack of data, concerns have been raised about the robustness and reproducibility of the predictions. This study presents the identification of robust and reproducible DCM signature genes based on the integration of several independent data sets and functional network information. Gene expression profiles from three public data sets containing DCM and non-DCM samples were integrated and analyzed, which allowed the implementation of clinical diagnostic models. Differentially expressed genes were evaluated in the context of a global protein–protein interaction network, constructed as part of this study. Potential associations with HF were identified by searching the scientific literature. From these analyses, classification models were built and their effectiveness in differentiating between DCM and non-DCM samples was estimated. The main outcome was a set of integrated, potentially novel DCM signature genes, which may be used as reliable disease biomarkers. An empirical demonstration of the power of the integrative classification models against single-source models is also given. 相似文献
1000.
Lim KH Collver HH Le YT Nagchowdhuri P Kenney JM 《Biochemical and biophysical research communications》2007,353(2):443-449
Major constituents of the amyloid plaques found in the brain of Alzheimer's patients are the 39-43 residue beta-amyloid (Abeta) peptides. Extensive in vitro as well as in vivo biochemical studies have shown that the 40- and 42-residue Abeta peptides play major roles in the neurodegenerative pathology of Alzheimer's disease. Although the two Abeta peptides share common aggregation properties, the 42-residue peptide is more amyloidogenic and more strongly associated with amyloid pathology. Thus, characterizations of the two Abeta peptides are of critical importance in understanding the molecular mechanism of Abeta amyloid formation. In this report, we present combined CD and NMR studies of the monomeric states of the two peptides under both non-amyloidogenic (<5 degrees C) and amyloid-forming conditions (>5 degrees C) at physiological pH. Our CD studies of the Abeta peptides showed that initially unfolded Abeta peptides at low temperature (<5 degrees C) gradually underwent conformational changes to more beta-sheet-like monomeric intermediate states at stronger amyloidogenic conditions (higher temperatures). Detailed residue-specific information on the structural transition was obtained by using NMR spectroscopy. Residues in the N-terminal (3-12) and 20-22 regions underwent conformational changes to more extended structures at the stronger amyloidogenic conditions. Almost identical structural transitions of those residues were observed in the two Abeta peptides, suggesting a similar amyloidogenic intermediate for the two peptides. The 42-residue Abeta (1-42) peptide was, however, more significantly structured at the C-terminal region (39-42), which may lead to the different aggregation propensity of the two peptides. 相似文献