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181.
182.
Rothbauer U Hofmann S Mühlenbein N Paschen SA Gerbitz KD Neupert W Brunner M Bauer MF 《The Journal of biological chemistry》2001,276(40):37327-37334
Tim8 and Tim13 of yeast belong to a family of evolutionary conserved zinc finger proteins that are organized in hetero-oligomeric complexes in the mitochondrial intermembrane space. Mutations in DDP1 (deafness dystonia peptide 1), the human homolog of Tim8, are associated with the Mohr-Tranebjaerg syndrome, a progressive neurodegenerative disorder. We show that DDP1 acts with human Tim13 in a complex in the intermembrane space. The DDP1.hTim13 complex is in direct contact with translocation intermediates of human Tim23 in mammalian mitochondria. The human DDP1.hTim13 complex complements the function of the TIM8.13 complex in yeast and facilitates import of yeast and human Tim23. Thus, the pathomechanism underlying the Mohr-Tranebjaerg syndrome may involve an impaired biogenesis of the human TIM23 complex causing severe pleiotropic mitochondrial dysfunction. 相似文献
183.
Hiltbrunner A Bauer J Vidi PA Infanger S Weibel P Hohwy M Kessler F 《The Journal of cell biology》2001,154(2):309-316
Chloroplast biogenesis requires the large-scale import of cytosolically synthesized precursor proteins. A trimeric translocon (Toc complex) containing two homologous GTP-binding proteins (atToc33 and atToc159) and a channel protein (atToc75) facilitates protein translocation across the outer envelope membrane. The mechanisms governing function and assembly of the Toc complex are not yet understood. This study demonstrates that atToc159 and its pea orthologue exist in an abundant, previously unrecognized soluble form, and partition between cytosol-containing soluble fractions and the chloroplast outer membrane. We show that soluble atToc159 binds directly to the cytosolic domain of atToc33 in a homotypic interaction, contributing to the integration of atToc159 into the chloroplast outer membrane. The data suggest that the function of the Toc complex involves switching of atToc159 between a soluble and an integral membrane form. 相似文献
184.
Swem LR Elsen S Bird TH Swem DL Koch HG Myllykallio H Daldal F Bauer CE 《Journal of molecular biology》2001,309(1):121-138
Recently, we demonstrated that the RegB/RegA two-component regulatory system from Rhodobacter capsulatus functions as a global regulator of metabolic processes that either generate or consume reducing equivalents. For example, the RegB/RegA system controls expression of such energy generating processes as photosynthesis and hydrogen utilization. In addition, RegB/RegA also control nitrogen and carbon fixation pathways that utilize reducing equivalents. Here, we use a combination of DNase I protection and plasmid-based reporter expression studies to demonstrate that RegA directly controls synthesis of cytochrome cbb3 and ubiquinol oxidases that function as terminal electron acceptors in a branched respiratory chain. We also demonstrate that RegA controls expression of cytochromes c2, c(y) and the cytochrome bc1 complex that are involved in both photosynthetic and respiratory electron transfer events. These data provide evidence that the RegB/RegA two-component system has a major role in controlling the synthesis of numerous processes that affect reducing equivalents in Rhodobacter capsulatus. 相似文献
185.
Mutagenesis of the Neisseria gonorrhoeae porin reduces invasion in epithelial cells and enhances phagocyte responsiveness 总被引:3,自引:0,他引:3
Porin (PorB), the major outer membrane protein of Neisseria gonorrhoeae, has been implicated in pathogenesis previously. However, the fact that porin deletion mutants are not viable has complicated investigations. Here, we describe a method of manipulating the porin gene site-specifically. N. gonorrhoeae MS11, which harbours the porB1B (P.1B) porin allele, was used to generate mutants carrying deletions in the surface loops 1 and 5. An 11-amino-acid deletion in loop 1 impaired Opa50-dependent invasion into human Chang epithelial cells, whereas loop 5 deletion exhibited no apparent phenotype. In a second approach, the complete gonococcal porB1B was replaced by the porBNia gene of Neisseria lactamica. Such mutants were unable to induce efficient uptake by epithelial cells but induced an enhanced respiratory response in HL60 phagocytic cells. The increased respiratory burst was accompanied by an enhanced phagocytic uptake of the mutant compared with the wild-type strain. Our data extend previous evidence for multiple central functions of PorB in the infection process. 相似文献
186.
C. A. Stella C. Korch E. H. Ramos A. Bauer R. Kölling J. R. Mattoon 《Molecular genetics and genomics : MGG》1999,262(2):332-341
Leucine uptake by Saccharomyces cerevisiae is mediated by three transport systems, the general amino acid transport system (GAP), encoded by GAP1, and two group-specific systems (S1 and S2), which also transport isoleucine and valine. A new mutant defective in both group-specific transport activities was isolated by employing a gap1 leu4 strain and selecting for trifluoroleucine-resistant mutants which also showed greatly reduced ability to utilize l-leucine as sole nitrogen source and very low levels of [14C]l-leucine uptake. A multicopy plasmid containing a DNA fragment which complemented the leucine transport defect was isolated by selecting for transformants that grew normally on minimal medium containing leucine as nitrogen source and subsequently assaying [14C]l-leucine uptake. Transformation of one such mutant, lep1, restored sensitivity to trifluoroleucine. The complementing gene, designated LEP1, was subcloned and sequenced. The LEP1 ORF encodes a large protein that lacks characteristics of a transporter or permease (i.e., lacks hydrophobic domains necessary for membrane association). Instead, Lep1p is a very basic protein (pI of 9.2) that contains a putative bipartite signal sequence for targeting to the nucleus, suggesting that it might be a DNA-binding protein. A database search revealed that LEP1 encodes a polypeptide that is identical to Sac3p except for an N-terminal truncation. The original identification of SAC3 was based on the isolation of a mutant allele, sac3-1, that suppresses the temperature-sensitive growth defect of an actin mutant containing the allele act1-1. Sac3p has been previously shown to be localized in the nucleus. When a lep1 mutant was crossed with a sac3 deletion mutant, no complementation was observed, indicating that the two mutations are functionally allelic. 相似文献
187.
The mitochondrial TIM22 preprotein translocase is highly conserved throughout the eukaryotic kingdom
Bauer MF Rothbauer U Mühlenbein N Smith RJ Gerbitz K Neupert W Brunner M Hofmann S 《FEBS letters》1999,464(1-2):41-47
The Mohr-Tranebjaerg syndrome (MTS), a neurodegenerative syndrome characterized by progressive sensorineural hearing loss, dystonia, mental retardation and blindness, is a mitochondrial disease caused by mutations in the deafness/dystonia peptide 1 (DDP1) gene. DDP1 shows similarity to the yeast proteins Tim9, Tim10 and Tim12, components of the mitochondrial import machinery for carrier proteins. Here, we show that DDP1 belongs to a large family of evolutionarily conserved proteins. We report the identification, chromosomal localization and expressional analysis of six human family members which represent further candidate genes for neurodegenerative diseases. 相似文献
188.
Phospholipase D stimulation by receptor tyrosine kinases mediated by protein kinase C and a Ras/Ral signaling cascade 总被引:6,自引:0,他引:6
Voss M Weernink PA Haupenthal S Möller U Cool RH Bauer B Camonis JH Jakobs KH Schmidt M 《The Journal of biological chemistry》1999,274(49):34691-34698
Stimulation of phospholipase D (PLD) in HEK-293 cells expressing the M(3) muscarinic receptor by phorbol ester-activated protein kinase C (PKC) apparently involves Ral GTPases. We report here that PKC, but not muscarinic receptor-induced PLD stimulation in these cells, is strongly and specifically reduced by expression of dominant-negative RalA, G26A RalA, as well as dominant-negative Ras, S17N Ras. In contrast, overexpression of the Ras-activated Ral-specific guanine nucleotide exchange factor, Ral-GDS, specifically enhanced PKC-induced PLD stimulation. Moreover, recombinant Ral-GDS potentiated Ral-dependent PKC-induced PLD stimulation in membranes. Epidermal growth factor, platelet-derived growth factor, and insulin, ligands for receptor tyrosine kinases (RTKs) endogenously expressed in HEK-293 cells, apparently use the PKC- and Ras/Ral-dependent pathway for PLD stimulation. First, PLD stimulation by the RTK agonists was prevented by PKC inhibition and PKC down-regulation. Second, expression of dominant-negative RalA and Ras mutants strongly reduced RTK-induced PLD stimulation. Third, overexpression of Ral-GDS largely potentiated PLD stimulation by the RTK agonists. Finally, using the Ral binding domain of the Ral effector RLIP as an activation-specific probe for Ral proteins, it is demonstrated that endogenous RalA is activated by phorbol ester and RTK agonists. Taken together, strong evidence is provided that RTK-induced PLD stimulation in HEK-293 cells is mediated by PKC and a Ras/Ral signaling cascade. 相似文献
189.
Bauer Paul J.; Schauf Heike; Schwarzer Andreas; Brown Joel E. 《American journal of physiology. Cell physiology》1999,276(3):C558
Na+/Ca2+exchange has been investigated in squid(Loligopealei) rhabdomeric membranes.Ca2+-containing vesicles have beenprepared from purified rhabdomeric membranes by extrusion throughpolycarbonate filters of 1-µm pore size. After removal of externalCa2+, up to 90% of the entrappedCa2+ could be specificallyreleased by the addition of Na+;this finding indicates that most of the vesicles containedNa+/Ca2+exchanger. The Na+-inducedCa2+ efflux had a half-maximumvalue (K1/2) of~44 mM and a Hill coefficient of ~1.7. The maximalNa+-inducedCa2+ efflux was ~0.6 nmolCa2+ · s1 · mgprotein1. SimilarNa+-inducedCa2+ effluxes were measured ifK+ was replaced withLi+ orCs+. Vesicles loaded withCa2+ byNa+/Ca2+exchange also released this Ca2+byNa+/Ca2+exchange, suggesting thatNa+/Ca2+exchange operated in both forward and reverse modes. Limited proteolysis by trypsin resulted in a rate ofCa2+ efflux enhanced byapproximately fivefold when efflux was activated with 95 mM NaCl. For vesicles subjected to limited proteolysis by trypsin,Na+/Ca2+exchange was characterized by aK1/2 of ~25 mMand a Hill coefficient of 1.6. For these vesicles, the maximalNa+-inducedCa2+ efflux was about twice asgreat as in control vesicles. We conclude thatNa+/Ca2+exchange proteins localized in rhabdomeric membranes mediate Ca2+ extrusion in squid photoreceptors. 相似文献
190.
A protein with a relative molecular mass of 31 kDa was specifically extracted by EGTA from a detergent-insoluble fraction of Giardia lamblia. N-terminal sequencing showed this protein to be identical to alpha 1-giardin, a component of the ventral disc which, based on its predicted amino acid sequence, has been classified as annexin XIX. Purified alpha 1-giardin associated with multilamellar phosphatidyl serine-containing vesicles in a Ca(2+)-dependent manner, confirming that it is a functional annexin. Molecular modelling of the amino acid sequence of the giardial annexin into the X-ray structure of annexin V suggests that the Ca(2+)-binding sites, which, as in other annexins, are all located on the convex surface of the molecule, are of the low-affinity type III. 相似文献