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1.
Olesen C  Picard M  Winther AM  Gyrup C  Morth JP  Oxvig C  Møller JV  Nissen P 《Nature》2007,450(7172):1036-1042
The sarcoplasmic reticulum Ca2+-ATPase, a P-type ATPase, has a critical role in muscle function and metabolism. Here we present functional studies and three new crystal structures of the rabbit skeletal muscle Ca2+-ATPase, representing the phosphoenzyme intermediates associated with Ca2+ binding, Ca2+ translocation and dephosphorylation, that are based on complexes with a functional ATP analogue, beryllium fluoride and aluminium fluoride, respectively. The structures complete the cycle of nucleotide binding and cation transport of Ca2+-ATPase. Phosphorylation of the enzyme triggers the onset of a conformational change that leads to the opening of a luminal exit pathway defined by the transmembrane segments M1 through M6, which represent the canonical membrane domain of P-type pumps. Ca2+ release is promoted by translocation of the M4 helix, exposing Glu 309, Glu 771 and Asn 796 to the lumen. The mechanism explains how P-type ATPases are able to form the steep electrochemical gradients required for key functions in eukaryotic cells.  相似文献   

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3.
Lee SJ  Matsuura Y  Liu SM  Stewart M 《Nature》2005,435(7042):693-696
Nuclear protein import is mediated mainly by the transport factor importin-beta that binds cytoplasmic cargo, most often via the importin-alpha adaptor, and then transports it through nuclear pore complexes. This active transport is driven by disassembly of the import complex by nuclear RanGTP. The switch I and II loops of Ran change conformation with nucleotide state, and regulate its interactions with nuclear trafficking components. Importin-beta consists of 19 HEAT repeats that are based on a pair of antiparallel alpha-helices (referred to as the A- and B-helices). The HEAT repeats stack to yield two C-shaped arches, linked together to form a helicoidal molecule that has considerable conformational flexibility. Here we present the structure of full-length yeast importin-beta (Kap95p or karyopherin-beta) complexed with RanGTP, which provides a basis for understanding the crucial cargo-release step of nuclear import. We identify a key interaction site where the RanGTP switch I loop binds to the carboxy-terminal arch of Kap95p. This interaction produces a change in helicoidal pitch that locks Kap95p in a conformation that cannot bind importin-alpha or cargo. We suggest an allosteric mechanism for nuclear import complex disassembly by RanGTP.  相似文献   

4.
Toyoshima C  Mizutani T 《Nature》2004,430(6999):529-535
P-type ATPases are ATP-powered ion pumps that establish ion concentration gradients across cell and organelle membranes. Here, we describe the crystal structure of the Ca2+ pump of skeletal muscle sarcoplasmic reticulum, a representative member of the P-type ATPase superfamily, with an ATP analogue, a Mg2+ and two Ca2+ ions in the respective binding sites. In this state, the ATP analogue reorganizes the three cytoplasmic domains (A, N and P), which are widely separated without nucleotide, by directly bridging the N and P domains. The structure of the P-domain itself is altered by the binding of the ATP analogue and Mg2+. As a result, the A-domain is tilted so that one of the transmembrane helices moves to lock the cytoplasmic gate of the transmembrane Ca2+-binding sites. This appears to be the mechanism for occluding the bound Ca2+ ions, before releasing them into the lumen of the sarcoplasmic reticulum.  相似文献   

5.
介绍了平衡式复合齿轮泵(马达)的工作原理,分析了复合齿轮泵流量特性,在此基础上设计出差动轮系式复合齿轮泵变量系统,并进行了分析。  相似文献   

6.
Toyoshima C  Nakasako M  Nomura H  Ogawa H 《Nature》2000,405(6787):647-655
Calcium ATPase is a member of the P-type ATPases that transport ions across the membrane against a concentration gradient. Here we have solved the crystal structure of the calcium ATPase of skeletal muscle sarcoplasmic reticulum (SERCA1a) at 2.6 A resolution with two calcium ions bound in the transmembrane domain, which comprises ten alpha-helices. The two calcium ions are located side by side and are surrounded by four transmembrane helices, two of which are unwound for efficient coordination geometry. The cytoplasmic region consists of three well separated domains, with the phosphorylation site in the central catalytic domain and the adenosine-binding site on another domain. The phosphorylation domain has the same fold as haloacid dehalogenase. Comparison with a low-resolution electron density map of the enzyme in the absence of calcium and with biochemical data suggests that large domain movements take place during active transport.  相似文献   

7.
为了准确分析YQH-100油气混输泵的叶片所受应力分布情况,运用Fluent软件与ANSYS软件协同仿真的方法对油气混输泵单级压缩级流道进行三维流动计算,将Fluent流场数据通过Workbench流固耦合技术传输给叶轮结构,再对叶轮叶片进行应力分析,通过数值分析确定叶片的应力及变形集中区域,得出叶片的应力及变形分布规律,并且可以看出运用流固耦合和不运用流固耦合时含气率对扬程和效率有较小的影响.  相似文献   

8.
六铝酸钙(CA6)材料具有优异的高温特性,在钢铁冶金等高温领域具有很大的应用潜力.然而,烧结过程CA6晶体的片状生长特性使其难以实现致密化,严重降低了该材料作为冶炼熔炉内衬的使用效果.本文基于CA6的应用领域和结构特点,对通过结构改性方法提高CA6致密度的研究现状进行了总结和分析,为CA6材料的性能提升和应用拓展提供参考.  相似文献   

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10.
Structural changes in glycogen phosphorylase induced by phosphorylation   总被引:27,自引:0,他引:27  
A comparison of the refined crystal structures of dimeric glycogen phosphorylase b and a reveals structural changes that represent the first step in the activation of the enzyme. On phosphorylation of serine-14, the N-terminus of each subunit assumes an ordered helical conformation and binds to the surface of the dimer. The consequent structural changes at the N- and C-terminal regions lead to strengthened interactions between subunits and alter the binding sites for allosteric effectors and substrates.  相似文献   

11.
以牛血清白蛋白(BSA)作为模型蛋白,通过浊度法研究BSA形成的无序蛋白聚集体的分解动力学并揭示其复杂结构细节.实验发现,BSA无序聚集体在碱性条件下分解过程有4个动力学阶段,包括1个快速的分解阶段,2个相对较慢的分解阶段和1个动力学惰性阶段.由此推测BSA聚集体中至少含有4种不同的BSA单体形态.  相似文献   

12.
Li L  Jose J  Xiang Y  Kuhn RJ  Rossmann MG 《Nature》2010,468(7324):705-708
Alphaviruses are enveloped RNA viruses that have a diameter of about 700?? and can be lethal human pathogens. Entry of virus into host cells by endocytosis is controlled by two envelope glycoproteins, E1 and E2. The E2-E1 heterodimers form 80 trimeric spikes on the icosahedral virus surface, 60 with quasi-three-fold symmetry and 20 coincident with the icosahedral three-fold axes arranged with T = 4 quasi-symmetry. The E1 glycoprotein has a hydrophobic fusion loop at one end and is responsible for membrane fusion. The E2 protein is responsible for receptor binding and protects the fusion loop at neutral pH. The lower pH in the endosome induces the virions to undergo an irreversible conformational change in which E2 and E1 dissociate and E1 forms homotrimers, triggering fusion of the viral membrane with the endosomal membrane and then releasing the viral genome into the cytoplasm. Here we report the structure of an alphavirus spike, crystallized at low pH, representing an intermediate in the fusion process and clarifying the maturation process. The trimer of E2-E1 in the crystal structure is similar to the spikes in the neutral pH virus except that the E2 middle region is disordered, exposing the fusion loop. The amino- and carboxy-terminal domains of E2 each form immunoglobulin-like folds, consistent with the receptor attachment properties of E2.  相似文献   

13.
D Pietrobon  B Prod'hom  P Hess 《Nature》1988,333(6171):373-376
The mechanism by which ions deliver their message to effector proteins involves a change in the protein conformation which is induced by the specific interaction of the ion with its binding site on the protein. In the case of an ion-channel protein, conformational changes induced by permeant ions and the consequences for channel function have received little attention. Here we report that binding of permeant cations to an intra-channel binding site of the dihydropyridine (DHP)-sensitive (L-type) Ca2+ channel leads to a conformational change which destabilizes the protonated state of a group on the external channel surface, and can shift its apparent pK value by more than 2 pH units. The lifetime of the protonated state correlates with the occupancy of an intra-channel binding site by the permeant cation. The demonstration of such conformational changes in a channel protein induced by the permeant ion has important implications for realistic models of the mechanism of ion permeation.  相似文献   

14.
J Bajorath  S Raghunathan  W Hinrichs  W Saenger 《Nature》1989,337(6206):481-484
The X-ray crystal structure of the subtilisin-type enzyme proteinase K at 1.5 A resolution shows that is has two binding sites for Ca2+. Scatchard analysis indicates that one Ca2+ binds tightly, with pK 7.6 x 10(-8) M-1, and the other only weakly. Although Ca2+ is not directly involved in the catalytic mechanism and is 16.6 A away from the alpha-carbon atoms of the catalytic triad Asp 39-His 69-Ser 224, the activity of proteinase K towards the synthetic substrate succinyl-Ala-Ala-Ala-p-nitroanilide drops slowly to approximately 20% of its original value when it is depleted of Ca2+. This is not due to autolysis of the enzyme. The X-ray crystal structure of Ca2+-free proteinase K shows that removal of Ca2+ from the tight binding site triggers a concerted domino-like movement of five peripheral loops and of two alpha-helices. At a distance of 25 A from this calcium-binding site, the geometry of both the secondary substrate binding site and of the catalytic triad is affected by this movement thereby reducing the activity of the enzyme.  相似文献   

15.
Rastogi VK  Girvin ME 《Nature》1999,402(6759):263-268
F1F0 ATP synthases use a transmembrane proton gradient to drive the synthesis of cellular ATP. The structure of the cytosolic F1 portion of the enzyme and the basic mechanism of ATP hydrolysis by F1 are now well established, but how proton translocation through the transmembrane F0 portion drives these catalytic changes is less clear. Here we describe the structural changes in the proton-translocating F0 subunit c that are induced by deprotonating the specific aspartic acid involved in proton transport. Conformational changes between the protonated and deprotonated forms of subunit c provide the structural basis for an explicit mechanism to explain coupling of proton translocation by F0 to the rotation of subunits within the core of F1. Rotation of these subunits within F1 causes the catalytic conformational changes in the active sites of F1 that result in ATP synthesis.  相似文献   

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用分光光度法和电位滴定法分别测定了对溴偶氮氯胂的六级离解常数 ,其值分别为 :pK1=1 10 ,pK2 =1 34,pK3 =3 4 4 ,pK4 =6 6 7,pK5=9 2 3,pK6=11 84 (分光光度法 ,572nm) ;pK3 =3 32 ,pK4 =6 72 ,pK5=9 89,pK6=11 6 1(电位滴定法 ) .  相似文献   

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俄罗斯姓名的文化伴随意义   总被引:2,自引:0,他引:2  
从词源意义、宗教意义、联想意义等三个侧面阐述了俄罗斯姓名的文化伴随意义,认为俄罗斯姓名的文化伴随意义具有强烈的民族性。认清这一点对姓名评价功能和感情评价功能的研究具有深远的意义。  相似文献   

20.
本文介绍了一种用往复泵组的泵效检测系统,应用微机对泵的有关参数进行自动采集,绘制示功图并计算输出有关泵组效卑的数据结果.  相似文献   

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