Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Escherichia coli Hsp40 DnaJ and Hsp70 DnaK cooperate in the binding of proteins at intermediate stages of folding, assembly, and translocation across membranes. Binding of protein substrates to the DnaK C-terminal domain is controlled by ATP binding and hydrolysis in the N-terminal ATPase domain. The interaction of DnaJ with DnaK is mediated at least in part by the highly conserved N-terminal J-domain of DnaJ that includes residues 2-75. Heteronuclear NMR experiments with uniformly 15N-enriched DnaJ2-75 indicate that the chemical environment of residues located in helix II and the flanking loops is perturbed on interaction with DnaK or a truncated DnaK molecule, DnaK2-388. NMR signals corresponding to these residues broaden and exhibit changes in chemical shifts in the presence of DnaK(MgADP). Addition of MgATP largely reversed the broadening, indicating that NMR signals of DnaJ2-75 respond to ATP-dependent changes in DnaK. The J-domain interaction is localized to the ATPase domain of DnaK and is likely to be dominated by electrostatic interactions. The results suggest that the J-domain tethers DnaK to DnaJ-bound substrates, which DnaK then binds with its C-terminal peptide-binding domain.
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PMID:Role of the J-domain in the cooperation of Hsp40 with Hsp70. 960 Sep 25

In this study, we demonstrate specific interaction of the GluR2 alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor subunit C-terminal peptide with an ATPase N-ethylmaleimide-sensitive fusion protein (NSF) and alpha- and beta-soluble NSF attachment proteins (SNAPs), as well as dendritic colocalization of these proteins. The assembly of the GluR2-NSF-SNAP complex is ATP hydrolysis reversible and resembles the binding of NSF and SNAP with the SNAP receptor (SNARE) membrane fusion apparatus. We provide evidence that the molar ratio of NSF to SNAP in the GluR2-NSF-SNAP complex is similar to that of the t-SNARE syntaxin-NSF-SNAP complex. NSF is known to disassemble the SNARE protein complex in a chaperone-like interaction driven by ATP hydrolysis. We propose a model in which NSF functions as a chaperone in the molecular processing of the AMPA receptor.
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PMID:The AMPA receptor GluR2 C terminus can mediate a reversible, ATP-dependent interaction with NSF and alpha- and beta-SNAPs. 969 55

Heat-shock protein 70 (Hsp70), one of the major molecular chaperones, has been shown to play a central role in many cellular processes. Heat-shock protein 40 (Hsp40) works as a co-chaperone for Hsp70. Hsp40, bound by unfolded polypeptide, can interact directly with Hsp70 to stimulate the ATPase activity of Hsp70. Hsp40 can also bind to unfolded polypeptides and prevent them from aggregating in vitro, thus acting as an independent molecular chaperone. The S. cerevisiae Hsp40 Sis1 C-terminal peptide-binding domain has been crystallized. The crystals diffract to 2.7 A and belong to space group P41212 or P43212 with a = 73.63, c = 80.16 A. The structure determination by the MAD method is under way.
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PMID:Purification, crystallization and preliminary X-ray crystallographic studies of S. cerevisiae Hsp40 Sis1. 1032 95

In the present study, we have used a non-denaturing gel electrophoresis assay to characterize the specificity of the peptide-induced depolymerization process of the isolated recombinant C-terminal domain (C30) of the molecular chaperone BiP, in the presence of specific synthetic peptides and with the neuropeptide Substance P. In the absence of peptidic ligand, C30 self-associates readily into multiple oligomeric species. Upon peptide addition, C30 oligomers convert into dimers, then into monomers. Our data indicate that the algorithm we previously developed to predict putative BiP binding sites in any protein sequence is also a good indicator as to whether a peptide can efficiently induce depolymerization of the C-terminal peptide binding domain and stimulate the ATPase activity of the full-length protein.
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PMID:Specificity of peptide-induced depolymerization of the recombinant carboxy-terminal fragment of BiP/GRP78. 1048 74

The plasma membrane Ca(2+)-ATPase (PMCA) plays an essential role in maintaining low cytosolic Ca(2+) in resting platelets. During platelet activation PMCA is phosphorylated transiently on tyrosine residues resulting in inhibition of the pump that enhances elevation of Ca(2+). Tyrosine phosphorylation of many proteins during platelet activation results in their association with the cytoskeleton. Consequently, in the present study we asked if PMCA interacts with the platelet cytoskeleton. We observed that very little PMCA is associated with the cytoskeleton in resting platelets but that approximately 80% of total PMCA (PMCA1b + PMCA4b) is redistributed to the cytoskeleton upon activation with thrombin. Tyrosine phosphorylation of PMCA during activation was not associated with the redistribution because tyrosine-phosphorylated PMCA was not translocated specifically to the cytoskeleton. Because PMCA b-splice isoforms have C-terminal PSD-95/Dlg/ZO-1 homology domain (PDZ)-binding domains, a C-terminal peptide was used to disrupt potential PDZ domain interactions. Activation of saponin-permeabilized platelets in the presence of the peptide led to a significant decrease of PMCA in the cytoskeleton. PMCA associated with the cytoskeleton retained Ca(2+)-ATPase activity. These results suggest that during activation active PMCA is recruited to the cytoskeleton by interaction with PDZ domains and that this association provides a microenvironment with a reduced Ca(2+) concentration.
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PMID:Plasma membrane Ca(2+)-ATPase associates with the cytoskeleton in activated platelets through a PDZ-binding domain. 1127 74

Heat-shock protein 70 (Hsp70) plays essential roles in a number of cellular processes such as protein folding, assembly and translocation. Heat-shock protein 40 (Hsp40) transiently interacts with Hsp70 and facilitates Hsp70 functions in these processes within cells. Hsp40 recognizes and binds non-native polypeptide and delivers it to Hsp70. Hsp40 can then stimulate the ATPase activity of Hsp70 to refold the polypeptide. To investigate the molecular mechanism by which Hsp40 interacts with Hsp70 to transport the non-native polypeptide, Saccharomyces cerevisiae Hsp40 Sis1 C-terminal peptide-binding fragment complexed with Hsp70 Ssa1 C-terminal lid domain has been produced and crystallized. The complex crystals diffract to 3.3 A and belong to the space group P4(1)2(1)2 or P4(3)2(1)2, with unit-cell parameters a = 112.17, c = 171.31 A. Structure determination by the MAD method is under way.
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PMID:Cloning, expression, purification and preliminary X-ray crystallographic studies of yeast Hsp40 Sis1 complexed with Hsp70 Ssa1 C-terminal lid domain. 1132 Mar 26

AAA proteins remodel other proteins to affect a multitude of biological processes. Their power to remodel substrates must lie in their capacity to couple substrate binding to conformational changes via cycles of nucleotide binding and hydrolysis, but these relationships have not yet been deciphered for any member. We report that when one AAA protein, Hsp104, engages polypeptide at the C-terminal peptide-binding region, the ATPase cycle of the C-terminal nucleotide-binding domain (NBD2) drives a conformational change in the middle region. This, in turn, drives ATP hydrolysis in the N-terminal ATPase domain (NBD1). This interdomain communication pathway can be blocked by mutation in the middle region or bypassed by antibodies that bind there, demonstrating the crucial role this region plays in transducing signals from one end of the molecule to the other.
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PMID:Defining a pathway of communication from the C-terminal peptide binding domain to the N-terminal ATPase domain in a AAA protein. 1198 67

In this study, the effect of pH on the conformation and the reactivity of the Escherichia coli Hsp70 molecular chaperone DnaK was investigated using spectroscopic and chemical assays. DnaK exhibits negligible binding of the hydrophobic dye 1-anilino-naphthalene-8-sulfonate (ANS) between pH 7 to 5.0, whereas appreciable binding occurs between pH 4.5 to 4.0. The binding of ANS to a protein is diagnostic of the presence of accessible ordered hydrophobic surfaces. Such hydrophobic surfaces are often displayed by partially folded protein intermediates such as molten globules. Nucleotide inhibits 70% of the ANS binding at pH 4.5 but none of the ANS binding at pH 4.0. Proteolysis of nucleotide-free DnaK at pH 4.5 with cathepsin D yields detectable fragments (masses > 20 kDa) of the C-terminal peptide-binding domain but none of the N-terminal ATPase domain, thus the ATPase domain is preferentially targeted for proteolysis. In contrast, proteolysis of nucleotide-free DnaK at pH 4.0 with cathepsin D cuts near the linker region, yielding both functional domains. Our interpretation of these data is that incubation of DnaK at pH 4.5 produces a partially unfolded form of the ATPase domain, in which secondary structure is mainly intact, but tertiary structure is reduced. Incubation of the protein at pH 4.0 produces an intermediate in which both functional domains have collapsed and possibly separated. Nucleotide inhibits the conformational change that occurs at pH 4.5 but not at 4.0.
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PMID:Characterization of two partially unfolded intermediates of the molecular chaperone DnaK at low pH. 1208 1

The N-terminus of the Na(+),K(+)-ATPase alpha-subunit shows some homology to that of Shaker-B K(+) channels; the latter has been shown to mediate the N-type channel inactivation in a ball-and-chain mechanism. When the Torpedo Na(+),K(+)-ATPase is expressed in Xenopus oocytes and the pump is transformed into an ion channel with palytoxin (PTX), the channel exhibits a time-dependent inactivation gating at positive potentials. The inactivation gating is eliminated when the N-terminus is truncated by deleting the first 35 amino acids after the initial methionine. The inactivation gating is restored when a synthetic N-terminal peptide is applied to the truncated pumps at the intracellular surface. Truncated pumps generate no electrogenic current and exhibit an altered stoichiometry for active transport. Thus, the N-terminus of the alpha-subunit appears to act like an inactivation gate and performs a critical step in the Na(+),K(+)-ATPase pumping function.
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PMID:Functional role of the N-terminus of Na(+),K(+)-ATPase alpha-subunit as an inactivation gate of palytoxin-induced pump channel. 1250 58

Sarco/endoplasmic reticulum-type calcium transport ATPases (SERCA enzymes) pump calcium ions from the cytosol into the endoplasmic reticulum. We report that in addition to the ubiquitously expressed SERCA2b isoform, a new splice variant of SERCA2 can be detected (SERCA2c) that arises from the inclusion of a short intronic sequence located between exons 20 and 21 of the SERCA2a isoform. Sequence analysis revealed classical splice donor and acceptor sites, as well as a branch-point site. Due to the presence in the new exon of an in-frame stop codon that is preceded by a 17 bp coding sequence, this mRNA potentially codes for a protein with a truncated C-terminus containing a short unique C-terminal peptide stretch. SERCA2c message was detected in epithelial, mesenchymal, and hematopoietic cell lines, as well as in primary human monocytes. Moreover, we found that during monocytic differentiation total SERCA2 ATPase expression is induced on the protein and mRNA level and that the novel SERCA2c messenger is also up-regulated during this process. These data indicate that the alternative splicing pattern of the 3(') region of the SERCA2 primary transcript is more complex than that previously thought and that this enzyme may be involved in the process of monocyte differentiation.
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PMID:Identification of a new SERCA2 splice variant regulated during monocytic differentiation. 1265 72


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