6 results on '"Geerlof, Arie"'
Search Results
2. The Mycobacterium Tuberculosis LipB Enzyme Functions as a Cysteine/Lysine Dyad Acyltransferase
- Author
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Ma, Qingjun, Zhao, Xin, Eddine, Ali Nasser, Geerlof, Arie, Li, Xinping, Cronan, John E., Kaufmann, Stefan H. E., and Wilmanns, Matthias
- Published
- 2006
- Full Text
- View/download PDF
3. The dynamics of linear polyubiquitin
- Author
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Jussupow, Alexander, Messias, Ana C., Stehle, Ralf, Geerlof, Arie, Solbak, Sara M. Ø., Paissoni, Cristina, Bach, Anders, Sattler, Michael, and Camilloni, Carlo
- Subjects
Astrophysics::High Energy Astrophysical Phenomena ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,Biophysics ,SciAdv r-articles ,macromolecular substances ,Biochemistry ,environment and public health ,Research Articles ,Research Article - Abstract
A new efficient method for SAXS-driven simulations allows researchers to explain the dynamics of linear polyubiquitin., Polyubiquitin chains are flexible multidomain proteins, whose conformational dynamics enable them to regulate multiple biological pathways. Their dynamic is determined by the linkage between ubiquitins and by the number of ubiquitin units. Characterizing polyubiquitin behavior as a function of their length is hampered because of increasing system size and conformational variability. Here, we introduce a new approach to efficiently integrating small-angle x-ray scattering with simulations allowing us to accurately characterize the dynamics of linear di-, tri-, and tetraubiquitin in the free state as well as of diubiquitin in complex with NEMO, a central regulator in the NF-κB pathway. Our results show that the behavior of the diubiquitin subunits is independent of the presence of additional ubiquitin modules and that the dynamics of polyubiquitins with different lengths follow a simple model. Together with experimental data from multiple biophysical techniques, we then rationalize the 2:1 NEMO:polyubiquitin binding.
- Published
- 2020
4. Trnp1 organizes diverse nuclear membrane‐less compartments in neural stem cells.
- Author
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Esgleas, Miriam, Falk, Sven, Forné, Ignasi, Thiry, Marc, Najas, Sonia, Zhang, Sirui, Mas‐Sanchez, Aina, Geerlof, Arie, Niessing, Dierk, Wang, Zefeng, Imhof, Axel, and Götz, Magdalena
- Subjects
NEURAL stem cells ,NUCLEAR proteins ,CELL cycle ,NUCLEOLUS ,NEURAL development ,BIOCHEMISTRY - Abstract
TMF1‐regulated nuclear protein 1 (Trnp1) has been shown to exert potent roles in neural development affecting neural stem cell self‐renewal and brain folding, but its molecular function in the nucleus is still unknown. Here, we show that Trnp1 is a low complexity protein with the capacity to phase separate. Trnp1 interacts with factors located in several nuclear membrane‐less organelles, the nucleolus, nuclear speckles, and condensed chromatin. Importantly, Trnp1 co‐regulates the architecture and function of these nuclear compartments in vitro and in the developing brain in vivo. Deletion of a highly conserved region in the N‐terminal intrinsic disordered region abolishes the capacity of Trnp1 to regulate nucleoli and heterochromatin size, proliferation, and M‐phase length; decreases the capacity to phase separate; and abrogates most of Trnp1 protein interactions. Thus, we identified Trnp1 as a novel regulator of several nuclear membrane‐less compartments, a function important to maintain cells in a self‐renewing proliferative state. Synopsis: How the developmental protein Trnp1 controls neural stem cell (NSC) self‐renewal and brain folding has remained unclear. A combination of biochemistry, super‐resolution microscopy and in vivo work now finds it to phase‐separate and orchestrate membrane‐less organelles (MLO) in the nucleus. Trnp1 self‐assembles and induces phase‐separated droplets.The conserved N‐terminal 16 amino acids of Trnp1 determine nucleolar size and NSC proliferation in the developing cortex.Trnp1 directly interacts with MLO proteins, regulating nucleoli, chromatin architecture and nuclear speckles.Trnp1 alters nucleolar dynamics during the cell cycle and shortens mitosis.Trnp1 affects MLO size and function including splicing and translation. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
5. Pitchfork and Gprasp2 Target Smoothened to the Primary Cilium for Hedgehog Pathway Activation.
- Author
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Jung, Bomi, Padula, Daniela, Burtscher, Ingo, Landerer, Cedric, Lutter, Dominik, Theis, Fabian, Messias, Ana C., Geerlof, Arie, Sattler, Michael, Kremmer, Elisabeth, Boldt, Karsten, Ueffing, Marius, and Lickert, Heiko
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CILIA & ciliary motion ,MEMBRANE proteins ,CHROMOSOMAL translocation ,HEDGEHOG signaling proteins ,G protein coupled receptors - Abstract
The seven-transmembrane receptor Smoothened (Smo) activates all Hedgehog (Hh) signaling by translocation into the primary cilia (PC), but how this is regulated is not well understood. Here we show that Pitchfork (Pifo) and the G protein-coupled receptor associated sorting protein 2 (Gprasp2) are essential components of an Hh induced ciliary targeting complex able to regulate Smo translocation to the PC. Depletion of Pifo or Gprasp2 leads to failure of Smo translocation to the PC and lack of Hh target gene activation. Together, our results identify a novel protein complex that is regulated by Hh signaling and required for Smo ciliary trafficking and Hh pathway activation. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
6. Galectin-3 Induces Clustering of CD147 and Integrin-β1 Transmembrane Glycoprotein Receptors on the RPE Cell Surface.
- Author
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Priglinger, Claudia S., Szober, Christoph M., Priglinger, Siegfried G., Merl, Juliane, Euler, Kerstin N., Kernt, Marcus, Gondi, Gabor, Behler, Jennifer, Geerlof, Arie, Kampik, Anselm, Ueffing, Marius, and Hauck, Stefanie M.
- Subjects
GALECTINS ,CD antigens ,INTEGRINS ,MEMBRANE proteins ,GLYCOPROTEIN receptors ,RHODOPSIN ,CELL membranes - Abstract
Proliferative vitreoretinopathy (PVR) is a blinding disease frequently occurring after retinal detachment surgery. Adhesion, migration and matrix remodeling of dedifferentiated retinal pigment epithelial (RPE) cells characterize the onset of the disease. Treatment options are still restrained and identification of factors responsible for the abnormal behavior of the RPE cells will facilitate the development of novel therapeutics. Galectin-3, a carbohydrate-binding protein, was previously found to inhibit attachment and spreading of retinal pigment epithelial cells, and thus bares the potential to counteract PVR-associated cellular events. However, the identities of the corresponding cell surface glycoprotein receptor proteins on RPE cells are not known. Here we characterize RPE-specific Gal-3 containing glycoprotein complexes using a proteomic approach. Integrin-β1, integrin-α3 and CD147/EMMPRIN, a transmembrane glycoprotein implicated in regulating matrix metalloproteinase induction, were identified as potential Gal-3 interactors on RPE cell surfaces. In reciprocal immunoprecipitation experiments we confirmed that Gal-3 associated with CD147 and integrin-β1, but not with integrin-α3. Additionally, association of Gal-3 with CD147 and integrin-β1 was observed in co-localization analyses, while integrin-α3 only partially co-localized with Gal-3. Blocking of CD147 and integrin-β1 on RPE cell surfaces inhibited binding of Gal-3, whereas blocking of integrin-α3 failed to do so, suggesting that integrin-α3 is rather an indirect interactor. Importantly, Gal-3 binding promoted pronounced clustering and co-localization of CD147 and integrin-β1, with only partial association of integrin-α3. Finally, we show that RPE derived CD147 and integrin-β1, but not integrin-α3, carry predominantly β-1,6-N-actyl-D-glucosamine-branched glycans, which are high-affinity ligands for Gal-3. We conclude from these data that extracellular Gal-3 triggers clustering of CD147 and integrin-β1 via interaction with β1,6-branched N-glycans on RPE cells and hypothesize that Gal-3 acts as a positive regulator for CD147/integrin-β1 clustering and therefore modifies RPE cell behavior contributing to the pathogenesis of PVR. Further investigations at this pathway may aid in the development of specific therapies for PVR. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
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