共查询到20条相似文献,搜索用时 15 毫秒
1.
Domain separation in the activation of glycogen phosphorylase a 总被引:3,自引:0,他引:3
E J Goldsmith S R Sprang R Hamlin N H Xuong R J Fletterick 《Science (New York, N.Y.)》1989,245(4917):528-532
The crystal structure of glycogen phosphorylase a complexed with its substrates, orthophosphate and maltopentaose, has been determined and refined at a resolution of 2.8 angstroms. With oligosaccaride bound at the glycogen storage site, the phosphate ion binds at the catalytic site and causes the regulatory and catalytic domains to separate with the loss of stabilizing interactions between them. Homotropic cooperativity between the active sites of the allosteric dimer results from rearrangements in isologous contacts between symmetry-related helices in the subunit interface. The conformational changes in the core of the interface are correlated with those observed on covalent activation by phosphorylation at Ser14 (phosphorylase b----a). 相似文献
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Structural basis for the activation of glycogen phosphorylase b by adenosine monophosphate 总被引:12,自引:0,他引:12
S R Sprang S G Withers E J Goldsmith R J Fletterick N B Madsen 《Science (New York, N.Y.)》1991,254(5036):1367-1371
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Calcium-induced activation of phosphorylase in rat hearts 总被引:1,自引:0,他引:1
Isolated perfused rat hearts exposed to increased calcium concentrations demonstrated a marked activation of phosphorylase, the maximum occurring about 15 seconds after the peak of the positive inotropic response. These observations provide an explanation for the failure of earlier investigations to demonstrate a significant calcium-induced increase in the active form of phosphorylase in the intact heart. 相似文献
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Tezcan FA Kaiser JT Mustafi D Walton MY Howard JB Rees DC 《Science (New York, N.Y.)》2005,309(5739):1377-1380
Adenosine triphosphate (ATP) hydrolysis in the nitrogenase complex controls the cycle of association and dissociation between the electron donor adenosine triphosphatase (ATPase) (Fe-protein) and its target catalytic protein (MoFe-protein), driving the reduction of dinitrogen into ammonia. Crystal structures in different nucleotide states have been determined that identify conformational changes in the nitrogenase complex during ATP turnover. These structures reveal distinct and mutually exclusive interaction sites on the MoFe-protein surface that are selectively populated, depending on the Fe-protein nucleotide state. A consequence of these different docking geometries is that the distance between redox cofactors, a critical determinant of the intermolecular electron transfer rate, is coupled to the nucleotide state. More generally, stabilization of distinct docking geometries by different nucleotide states, as seen for nitrogenase, could enable nucleotide hydrolysis to drive the relative motion of protein partners in molecular motors and other systems. 相似文献
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Lutz S Shankaranarayanan A Coco C Ridilla M Nance MR Vettel C Baltus D Evelyn CR Neubig RR Wieland T Tesmer JJ 《Science (New York, N.Y.)》2007,318(5858):1923-1927
The guanine nucleotide exchange factor p63RhoGEF is an effector of the heterotrimeric guanine nucleotide-binding protein (G protein) Galphaq and thereby links Galphaq-coupled receptors (GPCRs) to the activation of the small-molecular-weight G protein RhoA. We determined the crystal structure of the Galphaq-p63RhoGEF-RhoA complex, detailing the interactions of Galphaq with the Dbl and pleckstrin homology (DH and PH) domains of p63RhoGEF. These interactions involve the effector-binding site and the C-terminal region of Galphaq and appear to relieve autoinhibition of the catalytic DH domain by the PH domain. Trio, Duet, and p63RhoGEF are shown to constitute a family of Galphaq effectors that appear to activate RhoA both in vitro and in intact cells. We propose that this structure represents the crux of an ancient signal transduction pathway that is expected to be important in an array of physiological processes. 相似文献
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Robinson RC Mejillano M Le VP Burtnick LD Yin HL Choe S 《Science (New York, N.Y.)》1999,286(5446):1939-1942
The actin-binding protein gelsolin is involved in remodeling the actin cytoskeleton during growth-factor signaling, apoptosis, cytokinesis, and cell movement. Calcium-activated gelsolin severs and caps actin filaments. The 3.4 angstrom x-ray structure of the carboxyl-terminal half of gelsolin (G4-G6) in complex with actin reveals the basis for gelsolin activation. Calcium binding induces a conformational rearrangement in which domain G6 is flipped over and translated by about 40 angstroms relative to G4 and G5. The structural reorganization tears apart the continuous beta sheet core of G4 and G6. This exposes the actin-binding site on G4, enabling severing and capping of actin filaments to proceed. 相似文献
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Phototropins are light-activated kinases important for plant responses to blue light. Light initiates signaling in these proteins by generating a covalent protein-flavin mononucleotide (FMN) adduct within sensory Per-ARNT-Sim (PAS) domains. We characterized the light-dependent changes of a phototropin PAS domain by solution nuclear magnetic resonance spectroscopy and found that an alpha helix located outside the canonical domain plays a key role in this activation process. Although this helix associates with the PAS core in the dark, photoinduced changes in the domain structure disrupt this interaction. We propose that this mechanism couples light-dependent bond formation to kinase activation and identifies a signaling pathway conserved among PAS domains. 相似文献
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Sondermann H Scheufler C Schneider C Hohfeld J Hartl FU Moarefi I 《Science (New York, N.Y.)》2001,291(5508):1553-1557
Bag (Bcl2-associated athanogene) domains occur in a class of cofactors of the eukaryotic chaperone 70-kilodalton heat shock protein (Hsp70) family. Binding of the Bag domain to the Hsp70 adenosine triphosphatase (ATPase) domain promotes adenosine 5'-triphosphate-dependent release of substrate from Hsp70 in vitro. In a 1.9 angstrom crystal structure of a complex with the ATPase of the 70-kilodalton heat shock cognate protein (Hsc70), the Bag domain forms a three-helix bundle, inducing a conformational switch in the ATPase that is incompatible with nucleotide binding. The same switch is observed in the bacterial Hsp70 homolog DnaK upon binding of the structurally unrelated nucleotide exchange factor GrpE. Thus, functional convergence has allowed proteins with different architectures to trigger a conserved conformational shift in Hsp70 that leads to nucleotide exchange. 相似文献
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Phosphorylase kinase of the liver: deficiency in a girl with increased hepatic glycogen 总被引:4,自引:0,他引:4
Studies of a child with glycogenosis revealed an increased concentration of glycogen and low phosphorylase activity in her liver. Using mixtures of homogenates of the patient's liver and of normal liver, we found the low phosphorylase activity to be caused by a deficiency of phosphorylase kinase and not of hepatic phosphorylase. The fact that phosphorylase activity was restored to normal values by the addition of phosphorylase b kinase from rabbit muscle substantiates this conclusion. 相似文献
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CCAAT-enhancer binding protein: a component of a differentiation switch 总被引:95,自引:0,他引:95
The CCAAT-enhancer binding protein (C/EBP) has now been found to promote the terminal differentiation of adipocytes. During the normal course of adipogenesis, C/EBP expression is restricted to a terminal phase wherein proliferative growth is arrested, and specialized cell phenotype is first manifested. A conditional form of C/EBP was developed, making it feasible to test its capacity to regulate the differentiation of cultured adipocytes. Premature expression of C/EBP in adipoblasts caused a direct cessation of mitotic growth. Moreover, when abetted by the effects of three adipogenic hormones, C/EBP promoted terminal cell differentiation. Since C/EBP is expressed in a variety of tissues, it may have a fundamental role in regulating the balance between cell growth and differentiation in higher animals. 相似文献
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Complete nucleotide sequence of a replicating RNA molecule 总被引:19,自引:0,他引:19
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Purified outer segments of bovine rods exhibit phosphodiesterase activity against adenosine and guanosine cyclic 3',5'-monophosphates (cyclic AMP and cyclic GMP). The enzyme hydrolyzed cyclic GMP more rapidly than cyclic AMP at low substrate concentrations. The presence of high phosphodiesterase activity in this highly specialized organelle suggests that this enzyme may function in control of cyclic nucleotide concentration during visual excitation or adaptation. 相似文献
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Cyclic adenosine monphosphate, metabolites, and phosphorylase in neural tissue: a comparison a methods of fixation 总被引:2,自引:0,他引:2
Fixation of rat brain tissue by freeze-blowing, microwave irradiation, immersion of whole rats in liquid nitrogen, and decapitation into liquid nitrogen indicates that postmortem changes in metabolites and enzyme forms are minimal in freeze-blown brains. Cyclic adenosine monophosphate levels are lowest in microwave-irradiated brains, which has been interpreted by some investigators to indicate rapid fixation and minimal anoxia. However, the changes in phosphocreatine, adenosine triphosphate, lactate, and phosphorylase clearly demonstrate that fixation by freeze-blowing or immersion in liquid nitrogen more closely approximate the state in vivo. 相似文献
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Tyzio R Cossart R Khalilov I Minlebaev M Hübner CA Represa A Ben-Ari Y Khazipov R 《Science (New York, N.Y.)》2006,314(5806):1788-1792
We report a signaling mechanism in rats between mother and fetus aimed at preparing fetal neurons for delivery. In immature neurons, gamma-aminobutyric acid (GABA) is the primary excitatory neurotransmitter. We found that, shortly before delivery, there is a transient reduction in the intracellular chloride concentration and an excitatory-to-inhibitory switch of GABA actions. These events were triggered by oxytocin, an essential maternal hormone for labor. In vivo administration of an oxytocin receptor antagonist before delivery prevented the switch of GABA actions in fetal neurons and aggravated the severity of anoxic episodes. Thus, maternal oxytocin inhibits fetal neurons and increases their resistance to insults during delivery. 相似文献
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DIXON M 《Science (New York, N.Y.)》1960,132(3439):1548-1550
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