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Article ; Online: Showcasing Different G-Quadruplex Folds of a G-Rich Sequence: Between Rule-Based Prediction and Butterfly Effect.

Vianney, Yoanes Maria / Schröder, Nina / Jana, Jagannath / Chojetzki, Gregor / Weisz, Klaus

Journal of the American Chemical Society

2023 Volume 145, Issue 40, Page(s) 22194–22205

Abstract: In better understanding the interactions of G-quadruplexes in a cellular or noncellular environment ... limited by their remarkable structural diversity. A G-rich sequence related to a promoter sequence ... of the PDGFR-β nuclease hypersensitivity element (NHE) comprises a G ...

Abstract	In better understanding the interactions of G-quadruplexes in a cellular or noncellular environment, a reliable sequence-based prediction of their three-dimensional fold would be extremely useful, yet is often limited by their remarkable structural diversity. A G-rich sequence related to a promoter sequence of the PDGFR-β nuclease hypersensitivity element (NHE) comprises a G
MeSH term(s)	G-Quadruplexes ; Promoter Regions, Genetic ; Magnetic Resonance Spectroscopy ; Thermodynamics ; Receptor, Platelet-Derived Growth Factor beta/genetics ; Nucleic Acid Conformation
Chemical Substances	Receptor, Platelet-Derived Growth Factor beta (EC 2.7.10.1)
Language	English
Publishing date	2023-09-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3155-0
ISSN	1520-5126 ; 0002-7863
ISSN (online)	1520-5126
ISSN	0002-7863
DOI	10.1021/jacs.3c08336
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Article ; Online: Activation of G

Ebner, Julia K / König, Gabriele M / Kostenis, Evi / Siegert, Peter / Aktories, Klaus / Orth, Joachim H C

Bone

2019 Volume 127, Page(s) 592–601

Abstract: ... paralleled by a constitutive activation of the heterotrimeric G ...

Abstract	The human disease fibrodysplasia ossificans progressiva (FOP) is a rare and highly disabling disorder of extensive heterotopic bone growth that is caused by a point mutation (R206H) in the activation domain of Alk2, a BMP (bone morphogenic protein) type 1 receptor. The mutation leads to extensive BMP-signaling induced by Activin A, which is normally an antagonist for wildtype receptors, resulting in excessive and uncontrolled bone formation. Here, we studied the effects of Pasteurella multocida toxin (PMT), which activates osteoclasts and inhibits osteoblast activity, in C2C12 myoblasts expressing the mutant Alk2(R206H) receptor as model of FOP. In our study, we mainly used alkaline phosphatase (ALP) activity as marker to determine osteoblast differentiation. BMP-4 stimulated an increase in ALP activity in C2C12-Alk2wt and C2C12-Alk2(R206H) cells. By contrast, Activin A only induced ALP activity in C2C12-Alk2(R206H) cells. In both cases, PMT acted as a potent inhibitor of ALP activity. PMT-induced inhibition of ALP activity was paralleled by a constitutive activation of the heterotrimeric G
MeSH term(s)	Activins/metabolism ; Alkaline Phosphatase/metabolism ; Animals ; Bacterial Proteins/metabolism ; Bacterial Toxins/metabolism ; Bone Morphogenetic Protein 4/metabolism ; Calcium Signaling ; Cell Line ; GTP-Binding Protein alpha Subunits, Gq-G11/metabolism ; Mice ; Models, Biological ; Myoblasts/metabolism ; Myositis Ossificans/pathology ; Osteoblasts/metabolism ; Signal Transduction ; Smad Proteins/metabolism
Chemical Substances	Bacterial Proteins ; Bacterial Toxins ; Bone Morphogenetic Protein 4 ; Pasteurella multocida toxin ; Smad Proteins ; activin A ; Activins (104625-48-1) ; Alkaline Phosphatase (EC 3.1.3.1) ; GTP-Binding Protein alpha Subunits, Gq-G11 (EC 3.6.5.1)
Language	English
Publishing date	2019-07-31
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	632515-4
ISSN	1873-2763 ; 8756-3282
ISSN (online)	1873-2763
ISSN	8756-3282
DOI	10.1016/j.bone.2019.07.031
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Article ; Online: Expanding the Topological Landscape by a G-Column Flip of a Parallel G-Quadruplex.

Mohr, Swantje / Jana, Jagannath / Vianney, Yoanes Maria / Weisz, Klaus

Chemistry (Weinheim an der Bergstrasse, Germany)

2021 Volume 27, Issue 40, Page(s) 10437–10447

Abstract: Canonical G-quadruplexes can adopt a variety of different topologies depending on the arrangement ... of propeller, lateral, or diagonal loops connecting the four G-columns. A novel intramolecular G-quadruplex ... structure is derived through inversion of the last G-tract of a three-layered parallel fold, associated ...

Abstract	Canonical G-quadruplexes can adopt a variety of different topologies depending on the arrangement of propeller, lateral, or diagonal loops connecting the four G-columns. A novel intramolecular G-quadruplex structure is derived through inversion of the last G-tract of a three-layered parallel fold, associated with the transition of a single propeller into a lateral loop. The resulting (3+1) hybrid fold features three syn⋅anti⋅anti⋅anti G-tetrads with a 3'-terminal all-syn G-column. Although the ability of forming a duplex stem-loop between G-tracts seems beneficial for a propeller-to-lateral loop rearrangement, unmodified G-rich sequences resist folding into the new (3+1) topology. However, refolding can be driven by the incorporation of syn-favoring guanosine analogues into positions of the fourth G-stretch. The presented hybrid-type G-quadruplex structure as determined by NMR spectroscopy may provide for an additional scaffold in quadruplex-based technologies.
MeSH term(s)	G-Quadruplexes ; Guanosine ; Magnetic Resonance Spectroscopy ; Nucleic Acid Conformation
Chemical Substances	Guanosine (12133JR80S)
Language	English
Publishing date	2021-06-04
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1478547-X
ISSN	1521-3765 ; 0947-6539
ISSN (online)	1521-3765
ISSN	0947-6539
DOI	10.1002/chem.202101181
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Article ; Online: Guiding the folding of G-quadruplexes through loop residue interactions.

Jana, Jagannath / Vianney, Yoanes Maria / Schröder, Nina / Weisz, Klaus

Nucleic acids research

2022 Volume 50, Issue 12, Page(s) 7161–7175

Abstract: A G-rich sequence was designed to allow folding into either a stable parallel or hybrid-type ... thermodynamic understanding of delicate loop interactions in genomic and artificially designed quadruplexes, e.g ...

Abstract	A G-rich sequence was designed to allow folding into either a stable parallel or hybrid-type topology. With the parent sequence featuring coexisting species, various related sequences with single and double mutations and with a shortened central propeller loop affected the topological equilibrium. Two simple modifications, likewise introduced separately to all sequences, were employed to lock folds into one of the topologies without noticeable structural alterations. The unique combination of sequence mutations, high-resolution NMR structural information, and the thermodynamic stability for both topological competitors identified critical loop residue interactions. In contrast to first loop residues, which are mostly disordered and exposed to solvent in both propeller and lateral loops bridging a narrow groove, the last loop residue in a lateral three-nucleotide loop is engaged in stabilizing stacking interactions. The propensity of single-nucleotide loops to favor all-parallel topologies by enforcing a propeller-like conformation of an additional longer loop is shown to result from their preference in linking two outer tetrads of the same tetrad polarity. Taken together, the present studies contribute to a better structural and thermodynamic understanding of delicate loop interactions in genomic and artificially designed quadruplexes, e.g. when employed as therapeutics or in other biotechnological applications.
MeSH term(s)	Biotechnology ; Genomics ; Nucleotides
Chemical Substances	Nucleotides
Language	English
Publishing date	2022-06-27
Publishing country	England
Document type	Journal Article
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkac549
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Article ; Online: Impact of loop length and duplex extensions on the design of hybrid-type G-quadruplexes.

Jana, Jagannath / Vianney, Yoanes Maria / Weisz, Klaus

Chemical communications (Cambridge, England)

2024 Volume 60, Issue 7, Page(s) 854–857

Abstract: A G-rich core sequence G ...

Abstract	A G-rich core sequence G
Language	English
Publishing date	2024-01-18
Publishing country	England
Document type	Journal Article
ZDB-ID	1472881-3
ISSN	1364-548X ; 1359-7345 ; 0009-241X
ISSN (online)	1364-548X
ISSN	1359-7345 ; 0009-241X
DOI	10.1039/d3cc05625b
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Article ; Online: pH-Sensing G Protein-Coupled Receptor OGR1 (GPR68) Expression and Activation Increases in Intestinal Inflammation and Fibrosis.

de Vallière, Cheryl / Cosin-Roger, Jesus / Baebler, Katharina / Schoepflin, Anja / Mamie, Céline / Mollet, Michelle / Schuler, Cordelia / Bengs, Susan / Lang, Silvia / Scharl, Michael / Seuwen, Klaus / Ruiz, Pedro A / Hausmann, Martin / Rogler, Gerhard

International journal of molecular sciences

2022 Volume 23, Issue 3

Abstract: Local extracellular acidification occurs at sites of inflammation. Proton-sensing ovarian cancer G ...

Abstract	Local extracellular acidification occurs at sites of inflammation. Proton-sensing ovarian cancer G-protein-coupled receptor 1 (OGR1, also known as GPR68) responds to decreases in extracellular pH. Our previous studies show a role for OGR1 in the pathogenesis of mucosal inflammation, suggesting a link between tissue pH and immune responses. Additionally, pH-dependent signalling is associated with the progression of intestinal fibrosis. In this study, we aimed to investigate OGR1 expression and OGR1-mediated signalling in patients with inflammatory bowel disease (IBD). Our results show that OGR1 expression significantly increased in patients with IBD compared to non-IBD patients, as demonstrated by qPCR and immunohistochemistry (IHC). Paired samples from non-inflamed and inflamed intestinal areas of IBD patients showed stronger OGR1 IHC staining in inflamed mucosal segments compared to non-inflamed mucosa. IHC of human surgical samples revealed OGR1 expression in macrophages, granulocytes, endothelial cells, and fibroblasts. OGR1-dependent inositol phosphate (IP) production was significantly increased in CD14+ monocytes from IBD patients compared to healthy subjects. Primary human and murine fibroblasts exhibited OGR1-dependent IP formation, RhoA activation, F-actin, and stress fibre formation upon an acidic pH shift. OGR1 expression and signalling increases with IBD disease activity, suggesting an active role of OGR1 in the pathogenesis of IBD.
MeSH term(s)	Animals ; Endothelial Cells/metabolism ; Fibrosis ; Humans ; Hydrogen-Ion Concentration ; Inflammation ; Inflammatory Bowel Diseases/genetics ; Mice ; Receptors, G-Protein-Coupled/metabolism
Chemical Substances	GPR68 protein, human ; GPR68 protein, mouse ; Receptors, G-Protein-Coupled
Language	English
Publishing date	2022-01-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23031419
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Article ; Online: Ligand-Specific Allosteric Coupling Controls G-Protein-Coupled Receptor Signaling.

Holze, Janine / Bermudez, Marcel / Pfeil, Eva Marie / Kauk, Michael / Bödefeld, Theresa / Irmen, Matthias / Matera, Carlo / Dallanoce, Clelia / De Amici, Marco / Holzgrabe, Ulrike / König, Gabriele Maria / Tränkle, Christian / Wolber, Gerhard / Schrage, Ramona / Mohr, Klaus / Hoffmann, Carsten / Kostenis, Evi / Bock, Andreas

ACS pharmacology & translational science

2020 Volume 3, Issue 5, Page(s) 859–867

Abstract: Allosteric coupling describes a reciprocal process whereby G-protein-coupled receptors (GPCRs ...

Abstract	Allosteric coupling describes a reciprocal process whereby G-protein-coupled receptors (GPCRs) relay ligand-induced conformational changes from the extracellular binding pocket to the intracellular signaling surface. Therefore, GPCR activation is sensitive to both the type of extracellular ligand and intracellular signaling protein. We hypothesized that ligand-specific allosteric coupling may result in preferential (i.e., biased) engagement of downstream effectors. However, the structural basis underlying ligand-dependent control of this essential allosteric mechanism is poorly understood. Here, we show that two sets of extended muscarinic acetylcholine receptor M
Language	English
Publishing date	2020-09-02
Publishing country	United States
Document type	Journal Article
ISSN	2575-9108
ISSN (online)	2575-9108
DOI	10.1021/acsptsci.0c00069
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Article ; Online: Measurement of the bound-electron g-factor difference in coupled ions.

Sailer, Tim / Debierre, Vincent / Harman, Zoltán / Heiße, Fabian / König, Charlotte / Morgner, Jonathan / Tu, Bingsheng / Volotka, Andrey V / Keitel, Christoph H / Blaum, Klaus / Sturm, Sven

Nature

2022 Volume 606, Issue 7914, Page(s) 479–483

Abstract: Quantum electrodynamics (QED) is one of the most fundamental theories of physics and has been shown to be in excellent agreement with experimental ... ...

Abstract	Quantum electrodynamics (QED) is one of the most fundamental theories of physics and has been shown to be in excellent agreement with experimental results
Language	English
Publishing date	2022-06-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-022-04807-w
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Article ; Online: A Toolkit for Monitoring Immunoglobulin G Levels from Dried Blood Spots of Patients with Primary Immunodeficiencies.

Haberstroh, Hanna / Hirsch, Aleksandra / Goldacker, Sigune / Zessack, Norbert / Warnatz, Klaus / Grimbacher, Bodo / Salzer, Ulrich

Journal of clinical immunology

2023 Volume 43, Issue 6, Page(s) 1185–1192

Abstract: Purpose: This study assessed whether measuring immunoglobulin G (IgG) from dried blood spots (DBSs ...

Abstract	Purpose: This study assessed whether measuring immunoglobulin G (IgG) from dried blood spots (DBSs) using nephelometry is a suitable remote monitoring method for patients with primary immunodeficiencies (PID). Methods: Patients receiving immunoglobulin replacement therapy for PID were included in this non-interventional single-arm study (DRKS-ID: DRKS00020522) conducted in Germany from December 4, 2019, to December 22, 2020. Three blood samples, two capillary DBSs (one mail-transferred and the other direct-transferred to the laboratory), and one intravenous were collected from each patient. IgG levels were determined using nephelometry. IgG levels were summarized descriptively, and significant differences were assessed using Wilcoxon matched-pairs signed-rank tests. Correlation and agreement between IgG levels were assessed using Spearman correlation and Bland-Altman analyses, respectively. Results: Among 135 included patients, IgG levels measured from DBS samples were lower than those measured in serum (p < 0.0001). There was no significant difference between IgG levels in direct- and mail-transferred DBS samples. There was a high degree of correlation between IgG levels in serum samples and DBS samples (r = 0.94-0.95). Although there was a bias for higher levels of IgG in serum than in DBS samples, most samples were within the 95% interval of agreement. There was a high degree of correlation between IgG levels measured in direct- and mail-transferred DBS samples (r = 0.96) with no bias based on the shipment process and most samples within the 95% interval of agreement. Conclusion: Monitoring IgG levels from DBS samples is a suitable alternative to the standard method, and results are not substantially affected by mailing DBS cards.
MeSH term(s)	Humans ; Dried Blood Spot Testing/methods ; Immunoglobulin G ; Serum ; Germany
Chemical Substances	Immunoglobulin G
Language	English
Publishing date	2023-03-21
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	779361-3
ISSN	1573-2592 ; 0271-9142
ISSN (online)	1573-2592
ISSN	0271-9142
DOI	10.1007/s10875-023-01464-0
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Article: Statt eines Nachrufs: Nobel-Preis für Helm Stierlin?! Helm Stierlin im Gespräch mit Klaus G. Deissler

Stierlin, Helm / Deissler, Klaus G.

Zeitschrift für systemische Therapie und Beratung

2022 Volume 40, Issue 1, Page(s) 29

Language	German
Document type	Article
ZDB-ID	2132523-6
ISSN	1866-9875
Database	Current Contents Medicine

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