scholarly journals Hexa-histidin tag position influences disulfide structure but not binding behavior of in vitro folded N-terminal domain of rat corticotropin-releasing factor receptor type 2a

2004 ◽  
Vol 13 (9) ◽  
pp. 2470-2475 ◽  
Author(s):  
Jana Klose ◽  
Norbert Wendt ◽  
Sybille Kubald ◽  
Eberhard Krause ◽  
Klaus Fechner ◽  
...  
Keyword(s):  
Corticotropin Releasing Factor ◽  
Receptor Type ◽  
Binding Behavior ◽  
Terminal Domain ◽  
Disulfide Structure

scholarly journals A Balance Theory of Peripheral Corticotropin-Releasing Factor Receptor Type 1 and Type 2 Signaling to Induce Colonic Contractions and Visceral Hyperalgesia in Rats

Endocrinology ◽  
2014 ◽  
Vol 155 (12) ◽  
pp. 4655-4664 ◽  
Author(s):  
Tsukasa Nozu ◽  
Kaoru Takakusaki ◽  
Toshikatsu Okumura
Keyword(s):  
Colonic Motility ◽  
Corticotropin Releasing Factor ◽  
Receptor Type ◽  
In Vivo Studies ◽  
Induced Response ◽  
Visceral Hyperalgesia ◽  
Visceromotor Response

Several recent studies suggest that peripheral corticotropin-releasing factor (CRF) receptor type 1 (CRF1) and CRF2 have a counter regulatory action on gastrointestinal functions. We hypothesized that the activity balance of each CRF subtype signaling may determine the changes in colonic motility and visceral sensation. Colonic contractions were assessed by the perfused manometry, and contractions of colonic muscle strips were measured in vitro in rats. Visceromotor response was determined by measuring contractions of abdominal muscle in response to colorectal distensions (CRDs) (60 mm Hg for 10 min twice with a 30-min rest). All drugs were administered through ip route in in vivo studies. CRF increased colonic contractions. Pretreatment with astressin, a nonselective CRF antagonist, blocked the CRF-induced response, but astressin2-B, a selective CRF2 antagonist, enhanced the response by CRF. Cortagine, a selective CRF1 agonist, increased colonic contractions. In in vitro study, CRF increased contractions of muscle strips. Urocortin 2, a selective CRF2 agonist, itself did not alter the contractions but blocked this increased response by CRF. Visceromotor response to the second CRD was significantly higher than that of the first. Astressin blocked this CRD-induced sensitization, but astressin2-B or CRF did not affect it. Meanwhile, astressin2-B together with CRF significantly enhanced the sensitization. Urocortin 2 blocked, but cortagine significantly enhanced, the sensitization. These results indicated that peripheral CRF1 signaling enhanced colonic contractility and induced visceral sensitization, and these responses were modulated by peripheral CRF2 signaling. The activity balance of each subtype signaling may determine the colonic functions in response to stress.

Dimerization of Corticotropin-Releasing Factor Receptor Type 1 Is Not Coupled to Ligand Binding

2005 ◽  
Vol 25 (4-6) ◽  
pp. 251-276 ◽  
Author(s):  
OLIVER KRAETKE ◽  
BURKHARD WIESNER ◽  
JENNY EICHHORST ◽  
JENS FURKERT ◽  
MICHAEL BIENERT ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Corticotropin Releasing Factor ◽  
Receptor Type

scholarly journals EGCG binds intrinsically disordered N-terminal domain of p53 and disrupts p53-MDM2 interaction

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jing Zhao ◽  
Alan Blayney ◽  
Xiaorong Liu ◽  
Lauren Gandy ◽  
Weihua Jin ◽  
...  
Keyword(s):  
Large Scale ◽  
Molecular Mechanisms ◽  
Epigallocatechin Gallate ◽  
Cancer Drug ◽  
Dynamic Interactions ◽  
Cancer Drug Discovery ◽  
Intrinsically Disordered ◽  
Terminal Domain ◽  
Cancerous Cells

AbstractEpigallocatechin gallate (EGCG) from green tea can induce apoptosis in cancerous cells, but the underlying molecular mechanisms remain poorly understood. Using SPR and NMR, here we report a direct, μM interaction between EGCG and the tumor suppressor p53 (KD = 1.6 ± 1.4 μM), with the disordered N-terminal domain (NTD) identified as the major binding site (KD = 4 ± 2 μM). Large scale atomistic simulations (>100 μs), SAXS and AUC demonstrate that EGCG-NTD interaction is dynamic and EGCG causes the emergence of a subpopulation of compact bound conformations. The EGCG-p53 interaction disrupts p53 interaction with its regulatory E3 ligase MDM2 and inhibits ubiquitination of p53 by MDM2 in an in vitro ubiquitination assay, likely stabilizing p53 for anti-tumor activity. Our work provides insights into the mechanisms for EGCG’s anticancer activity and identifies p53 NTD as a target for cancer drug discovery through dynamic interactions with small molecules.

Dopamine effects the in vitro basal secretion of rat placenta opioids in an opioid and dopamine receptor type-specific manner

1996 ◽  
Vol 315 (1) ◽  
pp. 53-58 ◽  
Author(s):  
Constantine A. Stratakis ◽  
Nickolas S. Mitsiades ◽  
George P. Chrousos ◽  
Andrew N. Margioris
Keyword(s):  
Dopamine Receptor ◽  
Receptor Type ◽  
Basal Secretion ◽  
Specific Manner

Photoaffinity Cross-Linking of the Corticotropin-Releasing Factor Receptor Type 1 with Photoreactive Urocortin Analogues

Biochemistry ◽  
2005 ◽  
Vol 44 (47) ◽  
pp. 15569-15577 ◽  
Author(s):  
Oliver Kraetke ◽  
Brian Holeran ◽  
Hartmut Berger ◽  
Emanuel Escher ◽  
Michael Bienert ◽  
...  
Keyword(s):  
Corticotropin Releasing Factor ◽  
Receptor Type ◽  
Cross Linking

GnRH Release from the Mediobasal Hypothalamus: in vitro Inhibition by Corticotropin-Releasing Factor

1986 ◽  
Vol 43 (4) ◽  
pp. 533-536 ◽  
Author(s):  
Marco Gambacciani ◽  
Samuel S.C. Yen ◽  
Dennis D. Rasmussen
Keyword(s):  
Corticotropin Releasing Factor ◽  
Mediobasal Hypothalamus ◽  
Gnrh Release ◽  
In Vitro Inhibition

The C-terminal domain of Saccharomyces cerevisiae DNA topoisomerase II

1994 ◽  
Vol 14 (5) ◽  
pp. 3197-3207
Author(s):  
P R Caron ◽  
P Watt ◽  
J C Wang
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Nuclear Localization ◽  
Topoisomerase Ii ◽  
Dna Topoisomerase Ii ◽  
Dna Topoisomerase ◽  
Mutant Proteins ◽  
Terminal Domain ◽  
Catalytically Active

A set of carboxy-terminal deletion mutants of Saccharomyces cerevisiae DNA topoisomerase II were constructed for studying the functions of the carboxyl domain in vitro and in vivo. The wild-type yeast enzyme is a homodimer with 1,429 amino acid residues in each of the two polypeptides; truncation of the C terminus to Ile-1220 has little effect on the function of the enzyme in vitro or in vivo, whereas truncations extending beyond Gln-1138 yield completely inactive proteins. Several mutant enzymes with C termini in between these two residues were found to be catalytically active but unable to complement a top2-4 temperature-sensitive mutation. Immunomicroscopy results suggest that the removal of a nuclear localization signal in the C-terminal domain is likely to contribute to the physiological dysfunction of these proteins; the ability of these mutant proteins to relax supercoiled DNA in vivo shows, however, that at least some of the mutant proteins are present in the nuclei in a catalytically active form. In contrast to the ability of the catalytically active mutant proteins to relax supercoiled intracellular DNA, all mutants that do not complement the temperature-dependent lethality and high frequency of chromosomal nondisjunction of top2-4 were found to lack decatenation activity in vivo. The plausible roles of the DNA topoisomerase II C-terminal domain, in addition to providing a signal for nuclear localization, are discussed in the light of these results.

On mechanisms of colicin import: the outer membrane quandary

2018 ◽  
Vol 475 (23) ◽  
pp. 3903-3915 ◽  
Author(s):  
William A. Cramer ◽  
Onkar Sharma ◽  
S.D. Zakharov
Keyword(s):  
Outer Membrane ◽  
Catalytic Domain ◽  
Efflux Pump ◽  
Crystal Structure Analysis ◽  
Multidrug Efflux Pump ◽  
Terminal Domain ◽  
Colicin E1 ◽  
N Terminus ◽  
T Domain

Current problems in the understanding of colicin import across the Escherichia coli outer membrane (OM), involving a range of cytotoxic mechanisms, are discussed: (I) Crystal structure analysis of colicin E3 (RNAase) with bound OM vitamin B12 receptor, BtuB, and of the N-terminal translocation (T) domain of E3 and E9 (DNAase) inserted into the OM OmpF porin, provide details of the initial interaction of the colicin central receptor (R)- and N-terminal T-domain with OM receptors/translocators. (II) Features of the translocon include: (a) high-affinity (Kd ≈ 10−9 M) binding of the E3 receptor-binding R-domain E3 to BtuB; (b) insertion of disordered colicin N-terminal domain into the OmpF trimer; (c) binding of the N-terminus, documented for colicin E9, to the TolB protein on the periplasmic side of OmpF. Reinsertion of the colicin N-terminus into the second of the three pores in OmpF implies a colicin anchor site on the periplasmic side of OmpF. (III) Studies on the insertion of nuclease colicins into the cytoplasmic compartment imply that translocation proceeds via the C-terminal catalytic domain, proposed here to insert through the unoccupied third pore of the OmpF trimer, consistent with in vitro occlusion of OmpF channels by the isolated E3 C-terminal domain. (IV) Discussion of channel-forming colicins focuses mainly on colicin E1 for which BtuB is receptor and the OM TolC protein the proposed translocator. The ability of TolC, part of a multidrug efflux pump, for which there is no precedent for an import function, to provide a trans-periplasmic import pathway for colicin E1, is questioned on the basis of an unfavorable hairpin conformation of colicin N-terminal peptides inserted into TolC.

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