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41.
Association of the catalytic subunit of aspartate transcarbamoylase with a zinc-containing polypeptide fragment of the regulatory chain leads to increases in thermal stability. 总被引:1,自引:1,他引:0 下载免费PDF全文
C. B. Peterson B. B. Zhou D. Hsieh A. N. Creager H. K. Schachman 《Protein science : a publication of the Protein Society》1994,3(6):960-966
The regulatory enzyme aspartate transcarbamoylase (ATCase), comprising 2 catalytic (C) trimers and 3 regulatory (R) dimers, owes its stability to the manifold interchain interactions among the 12 polypeptide chains. With the availability of a recombinant 70-amino acid zinc-containing polypeptide fragment of the regulatory chain of ATCase, it has become possible to analyze directly the interaction between catalytic and regulatory chains in a complex of simpler structure independent of other interactions such as those between the 2 C trimers, which also contribute to the stability of the holoenzyme. Also, the effect of the interaction between the polypeptide, termed the zinc domain, and the C trimer on the thermal stability and other properties can be measured directly. Differential scanning microcalorimetry experiments demonstrated that the binding of the zinc domain to the C trimer leads to a complex of markedly increased thermal stability. This was shown with a series of mutant forms of the C trimer, which themselves varied greatly in their temperature of denaturation due to single amino acid replacements. With some C trimers, for which tm varied over a range of 30 degrees C due to diverse amino acid substitutions, the elevation of tm resulting from the interaction with the zinc domain was as large as 18 degrees C. The values of tm for a variety of complexes of mutant C trimers and the wild-type zinc domain were similar to those observed when the holoenzymes containing the mutant C trimers were subjected to heat denaturation.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
42.
劳为德 《生物化学与生物物理进展》1994,21(1):13-17
能组织成超级结构的各种序列组块,因其具有特定一级序列、或者具有某种卷曲的螺旋构象和某种非β螺旋结构,可以作为有特异功能的结构域、被特异的结合蛋白质识别和结合,因而可称为密码结构域,密码结构域作为特异的分子相互作用和过程的遗传指令,参与细胞周期的各种事件乃至发育和分化过程中基因有区别的表达. 相似文献
43.
The vegetation dynamics in two former braided channels of the Rhône River was studied at two time scales in order to test the following hypothesis: fluctuations would occur within seasons (flood disturbances, hydrological fluctuations, phenology) while successions would occur between years. The vegetation was surveyed in 1983, 1988 and 1989 during summer for the interannual investigation, and in spring 1989, summer 1989, winter 1989 and spring 1990 for the seasonal investigation. Terrestrialization, which was observed within the same period in other braided former channels of that river, did not happen here despite the 1989 drought. However, a vegetation zone situated in the upstream part one channel seems to represent some successional trend, resulting in the establishment of Nasturtium officinale and the increasing abundance of Chara vulgaris. In disagreement with the tested hypothesis, only fluctuations are observed at the two temporal scales in the other vegetation zones. The amplitude of cyclic trajectories observed in the seasonal study depends of the degree of hydraulic disturbances (floods, drought) that affects each vegetation zone. The channel that is closer to the river is maintained at a steady state by the periodical inputs of kinetic energy during river overflows and fast floods; the disturbances wash away fine deposits and rejuvenate the vegetation mosaic. In the other former channel that is less disturbed by floods and is characterized by a thick layer of fine sediments, the groundwater inputs from numerous limnocrene springs carry away organic matter and slow down ecological successions.Abbreviations C.A.
Correspondence Analysis 相似文献
44.
果树介壳虫寄生蜂资源的研究 总被引:4,自引:0,他引:4
介壳虫是果树的重要害虫,研究利用寄生蜂的自然控制作用是果树介壳虫生物防治和综合治理的重要途径。本论述了果树介壳虫寄生蜂资源的研究,报道了小蜂总科寄生蜂5科25属63种。 相似文献
45.
Abstract: Pretreatment with Triton X-100 more than doubled the binding of radiolabeled 5,7-dichlorokynurenic acid (DCKA), a proposed antagonist at a glycine (Gly) recognition domain on the N-methyl-d -aspartate (NMDA) receptor ionophore complex, in rat brain synaptic membranes. The binding exhibited an inverse temperature dependency, reversibility, and saturability, the binding sites consisting of a single component with a high affinity (27.5 nM) and a relatively low density (2.87 pmol/mg of protein). The binding of both [3H]DCKA and [3H]Gly was similarly displaced by numerous putative agonists and antagonists at the Gly domain in a concentration-dependent manner at a concentration range of 100 nM to 0.1 mM. Among the 24 putative ligands tested, DCKA was the second most potent displacer of the binding of both radioligands with no intrinsic affinity for the binding of [3H]kainic acid and α-amino-3-hydroxy-5-[3H]methylisoxazole-4-propionic acid (AMPA) to the non-NMDA receptors. In contrast, the other proposed potent Gly antagonist, 5,7-dinitroquinoxaline-2,3-dione, was active in displacing the binding of [3H]glutamic ([3H]Glu) and D,L-(E)-2-amino-4-[3H]propyl-5-phosphono-3-pentenoic acids to the NMDA recognition domain with a relatively high affinity for the non-NMDA receptors. In addition, the proposed antagonist at the AMPA-sensitive receptor, 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline, not only displaced weakly the binding of both [3H]- Gly and [3H]DCKA, but also inhibited the binding of (+)-5-[3H]methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine ([3H]MK-801) to an ion channel associated with the NMDA-sensitive receptor in the presence of added Glu alone in a manner sensitive to antagonism by further added Gly. Clear correlations were seen between potencies of the displacers to displace [3H]DCKA binding and [3H]Gly binding, in addition to between the potencies to displace [3H]-DCKA or [3H]Gly binding and to potentiate or inhibit [3H]MK-801 binding. All quinoxalines tested were invariably more potent displacers of [3H]DCKA binding than [3H]Gly binding, whereas kynurenines were similarly effective in displacing the binding of both [3H]Gly and [3H]-DCKA. These results undoubtedly give support to the proposal that [3H]DCKA is one useful radioligand available in terms of its high selectivity and affinity for the Gly domain in the brain. Possible multiplicity of the Gly domain is suggested by the differential pharmacological profiles between the binding of [3H]Gly and [3H]DCKA. 相似文献
46.
Diverse proteins that are 35% to 55% identical to actins have been discovered recently in yeasts, nematodes, and vertebrates.
In order to study these proteins systematically and relate their functions to those of conventional actins, we are isolating
the corresponding genes from the genetically tractable eukaryote,Drosophila melanogaster. Here we report the isolation and partial characterization of aDrosophila homologue of theSchizosaccharomyces pombe act2 gene. Degenerate oligonucleotide primers specifying peptides that are highly conserved within the actin protein superfamily
were used in conjunction with polymerase chain reaction (PCR) to amplify a portion of theDrosophila gene that we have namedactr66B. The corresponding full-length cDNA sequence encodes a protein of 418 residues that is 65% identical to the product of theS. pombe act2 gene, 80% identical to the bovineact2 homologue, but only 48% identical to the principalDrosophila cytoplasmic actin encoded by theAct5C actin gene. Alignment of the yeast, bovine, andDrosophila actin-related proteins shows that they have four peptide insertions, relative to conventional actins, three of which are
well placed to modify actin polymerization and one that is likely to perturb the binding of myosin. Locations of two of the
fiveactr66B introns are conserved betweenDrosophila and yeast genes, further attesting that they evolved from a common ancestor and are likely to encode proteins having similar
functions. We demonstrate that theDrosophila gene is located on the left arm of chromosome 3, within subdivision 66B. Finally, we show by RNA blot-hybridization that
the gene is expressed at low levels, relative to conventional nonmuscle actin, in all developmental stages. From these and
other observations we infer that the actr66B protein is a minor component of all cells, perhaps serving to modify the polymerization,
structure, and dynamic behavior of actin filaments.
Our work was supported by grants from the NIH and the Muscular Dystrophy Association to E.A.F.
Sequences described herein have been filed in the GenBank Database under Accession Number X71789. 相似文献
47.
The immunoglobulin G receptor FcRIIIB belongs to the immunoglobulin superfamily as two extracellular domains show homology to the immunoglobulin domains. Since some residues in these domains, such as the two cysteines, are supposed to form an intrachain disulfide bridge are so commonly conserved, they may be of importance for correct folding. Site-directed mutagenesis and expression in BHK21 confirmed this supposition for the FcRIIIB. Replacing both cysteines in the first and/or second domain by serines reduced the surface expression level by 50%, whereas the ligand binding capability was 20–30% of that seen in cells expressing the wild-type receptor. Replacing one of the four cysteines resulted in the loss of surface expression. Exchanging the conserved tryptophan in the first domain by phenylalanine only slightly affected the ligand binding (25%), whereas the surface expression remained unchanged. 相似文献
48.
49.
Peptide-protein interaction markedly alters the functional properties of the catalytic subunit of aspartate transcarbamoylase. 总被引:3,自引:3,他引:0 下载免费PDF全文
B. B. Zhou H. K. Schachman 《Protein science : a publication of the Protein Society》1993,2(1):103-112
Interaction of a 70-amino acid zinc-binding polypeptide from the regulatory chain of aspartate transcarbamoylase (ATCase) with the catalytic (C) subunit leads to dramatic changes in enzyme activity and affinity for ligand binding at the active sites. The complex between the polypeptide (zinc domain) and wild-type C trimer exhibits hyperbolic kinetics in contrast to the sigmoidal kinetics observed with the intact holoenzyme. Moreover, the Scatchard plot for binding N-(phosphonacetyl)-L-aspartate (PALA) to the complex is linear with a Kd corresponding to that evaluated for the holoenzyme converted to the relaxed (R) state. Additional evidence that the binding of the zinc domain to the C trimer converts it to the R state was attained with a mutant form of ATCase in which Lys 164 in the catalytic chain is replaced by Glu. As shown previously (Newell, J.O. & Schachman, H.K., 1990, Biophys. Chem. 37, 183-196), this mutant holoenzyme, which exists in the R conformation even in the absence of active site ligands, has a 50-fold greater affinity for PALA than the free C subunit. Adding the zinc domain to the C trimer containing the Lys 164-->Glu substitution leads to a 50-fold enhancement in the affinity for the bisubstrate analog yielding a value of Kd equal to that for the holoenzyme. A different mutant ATCase containing the Gln 231 to Ile replacement was shown (Peterson, C.B., Burman, D.L., & Schachman, H.K., 1992, Biochemistry 31, 8508-8515) to be much less active as a holoenzyme than as the free C trimer. For this mutant holoenzyme, the addition of substrates does not cause its conversion to the R state. However, the addition of the zinc domain to the Gln 231-->Ile C trimer leads to a marked increase in enzyme activity, and PALA binding data indicate that the complex resembles the R state of the holoenzyme. This interaction leading to a more active conformation serves as a model of intergenic complementation in which peptide binding to a protein causes a conformational correction at a site remote from the interacting surfaces resulting in activation of the protein. This linkage was also demonstrated by difference spectroscopy using a chromophore covalently bound at the active site, which served as a spectral probe for a local conformational change. The binding of ligands at the active sites was shown also to lead to a strengthening of the interaction between the zinc domain and the C trimer. 相似文献
50.
BackgroundA copper chaperone CCS is a multi-domain protein that supplies a copper ion to Cu/Zn-superoxide dismutase (SOD1). Among the domains of CCS, the N-terminal domain (CCSdI) belongs to a heavy metal-associated (HMA) domain, in which a Cys-x-x-Cys (CxxC) motif binds a heavy metal ion. It has hence been expected that the HMA domain in CCS has a role in the metal trafficking; however, the CxxC motif in the domain is dispensable for supplying a copper ion to SOD1, leaving an open question on roles of CCSdI in CCS.MethodsTo evaluate protein-protein interactions of CCS through CCSdI, yeast two-hybrid assay, a pull-down assay using recombinant proteins, and the analysis with fluorescence resonance energy transfer were performed.ResultsWe found that CCS specifically interacted with another copper chaperone HAH1, a HMA domain protein, through CCSdI. The interaction between CCSdI and HAH1 was not involved in the copper supply from CCS to SOD1 but was mediated by a zinc ion ligated with Cys residues of the CxxC motifs in CCSdI and HAH1.ConclusionWhile physiological significance of the interaction between copper chaperones awaits further investigation, we propose that CCSdI would have a role in the metal-mediated interaction with other proteins including heterologous copper chaperones. 相似文献