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71.
Viviane Richter Catherine S. Palmer Laura D. Osellame Abeer P. Singh Kirstin Elgass David A. Stroud Hiromi Sesaki Marc Kvansakul Michael T. Ryan 《The Journal of cell biology》2014,204(4):477-486
Mitochondrial fission is important for organelle transport, inheritance, and turnover, and alterations in fission are seen in neurological disease. In mammals, mitochondrial fission is executed by dynamin-related protein 1 (Drp1), a cytosolic guanosine triphosphatase that polymerizes and constricts the organelle. Recruitment of Drp1 to mitochondria involves receptors including Mff, MiD49, and MiD51. MiD49/51 form foci at mitochondrial constriction sites and coassemble with Drp1 to drive fission. Here, we solved the crystal structure of the cytosolic domain of human MiD51, which adopts a nucleotidyltransferase fold. Although MiD51 lacks catalytic residues for transferase activity, it specifically binds guanosine diphosphate and adenosine diphosphate. MiD51 mutants unable to bind nucleotides were still able to recruit Drp1. Disruption of an additional region in MiD51 that is not part of the nucleotidyltransferase fold blocked Drp1 recruitment and assembly of MiD51 into foci. MiD51 foci are also dependent on the presence of Drp1, and after scission they are distributed to daughter organelles, supporting the involvement of MiD51 in the fission apparatus. 相似文献
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Maren Kirstin Schuhmacher Monica Rolando Alexander Bröhm Sara Weirich Srikanth Kudithipudi Carmen Buchrieser Albert Jeltsch 《Journal of molecular biology》2018,430(13):1912-1925
RomA is a SET-domain containing protein lysine methyltransferase encoded by the Gram-negative bacterium Legionella pneumophila. It is exported into human host cells during infection and has been previously shown to methylate histone H3 at lysine 14 [Rolando et al. (2013), Cell Host Microbe, 13, 395–405]. Here, we investigated the substrate specificity of RomA on peptide arrays showing that it mainly recognizes a G-K-X-(PA) sequence embedded in a basic amino acid sequence context. Based on the specificity profile, we searched for possible additional RomA substrates in the human proteome and identified 34 novel peptide substrates. For nine of these, the corresponding full-length protein or protein domains could be cloned and purified. Using radioactive and antibody-based methylation assays, we showed that seven of them are methylated by RomA, four of them strongly, one moderately, and two weakly. Mutagenesis confirmed for the seven methylated proteins that methylation occurs at target lysine residues fitting to the specificity profile. Methylation of one novel substrate (AROS) was investigated in HEK293 cells overexpressing RomA and during infection with L. pneumophila. Methylation could be detected in both conditions, confirming that RomA methylates non-histone proteins in human cells. Our data show that the bacterial methyltransferase RomA methylates also human non-histone proteins suggesting a multifaceted role in the infection process. 相似文献
74.
A spatial genetics approach to inform vector control of tsetse flies (Glossina fuscipes fuscipes) in Northern Uganda 下载免费PDF全文
Norah Saarman Robert Opiro Chaz Hyseni Richard Echodu Kirstin Dion Elizabeth A. Opiyo Augustine W. Dunn Giuseppe Amatulli Serap Aksoy Adalgisa Caccone 《Ecology and evolution》2018,8(11):5336-5354
Tsetse flies (genus Glossina) are the only vector for the parasitic trypanosomes responsible for sleeping sickness and nagana across sub‐Saharan Africa. In Uganda, the tsetse fly Glossina fuscipes fuscipes is responsible for transmission of the parasite in 90% of sleeping sickness cases, and co‐occurrence of both forms of human‐infective trypanosomes makes vector control a priority. We use population genetic data from 38 samples from northern Uganda in a novel methodological pipeline that integrates genetic data, remotely sensed environmental data, and hundreds of field‐survey observations. This methodological pipeline identifies isolated habitat by first identifying environmental parameters correlated with genetic differentiation, second, predicting spatial connectivity using field‐survey observations and the most predictive environmental parameter(s), and third, overlaying the connectivity surface onto a habitat suitability map. Results from this pipeline indicated that net photosynthesis was the strongest predictor of genetic differentiation in G. f. fuscipes in northern Uganda. The resulting connectivity surface identified a large area of well‐connected habitat in northwestern Uganda, and twenty‐four isolated patches on the northeastern margin of the G. f. fuscipes distribution. We tested this novel methodological pipeline by completing an ad hoc sample and genetic screen of G. f. fuscipes samples from a model‐predicted isolated patch, and evaluated whether the ad hoc sample was in fact as genetically isolated as predicted. Results indicated that genetic isolation of the ad hoc sample was as genetically isolated as predicted, with differentiation well above estimates made in samples from within well‐connected habitat separated by similar geographic distances. This work has important practical implications for the control of tsetse and other disease vectors, because it provides a way to identify isolated populations where it will be safer and easier to implement vector control and that should be prioritized as study sites during the development and improvement of vector control methods. 相似文献
75.
Annette M. Griffin Kirstin J. Edwards Victor J. Morris Michael J. Gasson 《Biotechnology letters》1997,19(5):469-474
Analysis of the nucleotide sequence of a 1592 bp region of Acetobacter xylinum genomic DNA involved in acetan biosynthesis
revealed the presence of an open-reading frame (aceM) encoding a protein of 449 amino acids with a molecular weight of 48.5
kDa. The deduced amino acid sequence of aceM displayed high homology to the protein sequences of genes encoding UDP-glucose
dehydrogenase (UGDH) activities from other organisms. AceM is likely to encode the UGDH involved in the biosynthesis of UDP-glucuronic
acid required for acetanbiosynthesis.
This revised version was published online in November 2006 with corrections to the Cover Date. 相似文献
76.
77.
Kirstin Clark Nichols 《International journal for parasitology》1975,5(5):475-482
Udonella caligorum is acknowledged as a monogenean by some (Baer & Euzet, 1961; Yamaguti, 1963), but not by others (Ivanov, 1952; Bychowsky, 1957). It also has many similarities to Temnocephala, a rhabdocoel turbellarian. Light and electron microscope studies showed that the posterior sucker is glandular and that neither the adult nor eggs possess hooks; the head-gland secretion is eosinophilic and granular, and the tegument composed primarily of secretory granules and mitochondria. Ten pair of cells appearing to be paranephrocytes are present. Udonella larvae were shown to be larger than the host copepod nauplii, so transmission of worms between hosts must occur either during host mating, casual contact of hosts, or through free worms on the surface of the fish which the copepod infests. 相似文献
78.
Alexander W. Fischer Kirstin Albers Christian Schlein Frederike Sass Lucia M. Krott Hartwig Schmale Philip L.S.M. Gordts Ludger Scheja Joerg Heeren 《生物化学与生物物理学报:疾病的分子基础》2019,1865(6):1592-1603
The phosphotyrosine interacting domain-containing protein 1 (PID1) serves as a cytosolic adaptor protein of the LDL receptor-related protein 1 (LRP1). By regulating its intracellular trafficking, PID1 controls the hepatic, LRP1-dependent clearance of pro-atherogenic lipoproteins. In adipose and muscle tissues, LRP1 is present in endosomal storage vesicles containing the insulin-responsive glucose transporter 4 (GLUT4). This prompted us to investigate whether PID1 modulates GLUT4 translocation and function via its interaction with the LRP1 cytosolic domain. We initially evaluated this in primary brown adipocytes as we observed an inverse correlation between brown adipose tissue glucose uptake and expression of LRP1 and PID1. Insulin stimulation in wild type brown adipocytes induced LRP1 and GLUT4 translocation from endosomal storage vesicles to the cell surface. Loss of PID1 expression in brown adipocytes prompted LRP1 and GLUT4 sorting to the plasma membrane independent of insulin signaling. When placed on a diabetogenic high fat diet, systemic and adipocyte-specific PID1-deficient mice presented with improved hyperglycemia and glucose tolerance as well as reduced basal plasma insulin levels compared to wild type control mice. Moreover, the improvements in glucose parameters associated with increased glucose uptake in adipose and muscle tissues from PID1-deficient mice. The data provide evidence that PID1 serves as an insulin-regulated retention adaptor protein controlling translocation of LRP1 in conjunction with GLUT4 to the plasma membrane of adipocytes. Notably, loss of PID1 corrects for insulin resistance-associated hyperglycemia emphasizing its pivotal role and therapeutic potential in the regulation of glucose homeostasis. 相似文献
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80.
Novel Nox inhibitor of oxLDL-induced reactive oxygen species formation in human endothelial cells 总被引:5,自引:0,他引:5
Stielow C Catar RA Muller G Wingler K Scheurer P Schmidt HH Morawietz H 《Biochemical and biophysical research communications》2006,344(1):200-205
In this study, we investigated effects of a novel NAD(P)H oxidase (Nox)-inhibitor 3-benzyl-7-(2-benzoxazolyl)thio-1,2,3-triazolo[4,5-d]pyrimidine (VAS2870) on oxidized low-density lipoprotein (oxLDL)-mediated reactive oxygen species (ROS) formation in human endothelial cells. Primary cultures of human umbilical vein endothelial cells were cultured to confluence and ROS formation was induced with 50microg/ml oxLDL for 2h. ROS formation was detected by chemiluminescence (CL) using the Diogenes reagent. OxLDL induced ROS formation in human endothelial cells (171+/-12%; n=10, P<0.05 vs. control). This augmented ROS formation in response to oxLDL was completely inhibited by the Nox inhibitor VAS2870 (101+/-9%; n=7, P<0.05 vs. oxLDL). Similar results were obtained with superoxide dismutase (91+/-7%; n=7, P<0.05 vs. oxLDL). However, the Nox4 mRNA expression level was neither changed by oxLDL nor VAS2870. We conclude that VAS2870 could provide a novel strategy to inhibit the augmented endothelial superoxide anion formation in response to cardiovascular risk factors. 相似文献