scholarly journals Conformational landscape alternations promote oncogenic activities of Ras-related C3 botulinum toxin substrate 1 as revealed by NMR

2019 ◽  
Vol 5 (3) ◽  
pp. eaav8945 ◽  
Author(s):  
Yuki Toyama ◽  
Kenji Kontani ◽  
Toshiaki Katada ◽  
Ichio Shimada

Ras-related C3 botulinum toxin substrate 1 (Rac1) plays critical roles in the maintenance of cell morphology by cycling between inactive guanosine diphosphate (GDP)–bound and active guanosine triphosphate (GTP)–bound states. Rac1 P29S mutant is known to strongly promote oncogenesis by facilitating its intrinsic GDP dissociation and thereby increasing the level of the GTP-bound state. Here, we used solution nuclear magnetic resonance spectroscopy to investigate the activation mechanism of the oncogenic P29S mutant. We demonstrate that the conformational landscape is markedly altered in the mutant, and the preexisting equilibrium is shifted toward the conformation with reduced affinity for Mg2+, a cofactor that is critical for maintaining stable GDP binding. Our results suggest that the alternation of the preexisting conformational equilibrium of proteins is one of the fundamental mechanisms underlying their oncogenic activities.


2019 ◽  
Vol 5 (8) ◽  
pp. eaax1595
Author(s):  
Yuki Toyama ◽  
Kenji Kontani ◽  
Toshiaki Katada ◽  
Ichio Shimada

Ras-related C3 botulinum toxin substrate 1 (Rac1) functions as a molecular switch by cycling between an inactive guanosine diphosphate (GDP)–bound state and an active guanosine triphosphate (GTP)–bound state. An oncogenic mutant of Rac1, an N92I mutant, strongly promotes cell proliferation and subsequent oncogenic activities by facilitating the intrinsic GDP dissociation in the inactive GDP-bound state. Here, we used solution nuclear magnetic resonance spectroscopy to investigate the activation mechanism of the N92I mutant. We found that the static structure of the GDP binding site is not markedly perturbed by the mutation, but the overall conformational stability decreases in the N92I mutant, which then facilitates GDP dissociation by lowering the activation energy for the dissociation reaction. On the basis of these results, we proposed the activation mechanism of the N92I mutant, in which the decreased conformational stability plays important roles in its activation process.



2020 ◽  
Vol 35 (23) ◽  
pp. 2050140
Author(s):  
Eduardo López ◽  
Clara Rojas

We solve the one-dimensional time-independent Klein–Gordon equation in the presence of a smooth potential well. The bound state solutions are given in terms of the Whittaker [Formula: see text] function, and the antiparticle bound state is discussed in terms of potential parameters.



2005 ◽  
Vol 14 (06) ◽  
pp. 931-947 ◽  
Author(s):  
F. PILOTTO ◽  
M. DILLIG

We investigate the influence of retardation effects on covariant 3-dimensional wave functions for bound hadrons. Within a quark-(scalar) diquark representation of a baryon, the four-dimensional Bethe–Salpeter equation is solved for a 1-rank separable kernel which simulates Coulombic attraction and confinement. We project the manifestly covariant bound state wave function into three dimensions upon integrating out the non-static energy dependence and compare it with solutions of three-dimensional quasi-potential equations obtained from different kinematical projections on the relative energy variable. We find that for long-range interactions, as characteristic in QCD, retardation effects in bound states are of crucial importance.



1992 ◽  
Vol 07 (09) ◽  
pp. 1935-1951 ◽  
Author(s):  
G.A. KOZLOV

A systematic discussion of the probability of eta and KL bound-state decays—[Formula: see text] and [Formula: see text](l=e, μ)—within a three-dimensional reduction to the two-body quantum field theory is presented. The bound-state vertex function depends on the relative momentum of constituent-like particles. A structure-transition form factor is defined by a confinement-type quark-antiquark wave function. The phenomenology of this kind of decays is analyzed.



eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Marcel J Tauchert ◽  
Jean-Baptiste Fourmann ◽  
Reinhard Lührmann ◽  
Ralf Ficner

The DEAH-box helicase Prp43 is a key player in pre-mRNA splicing as well as the maturation of rRNAs. The exact modus operandi of Prp43 and of all other spliceosomal DEAH-box RNA helicases is still elusive. Here, we report crystal structures of Prp43 complexes in different functional states and the analysis of structure-based mutants providing insights into the unwinding and loading mechanism of RNAs. The Prp43•ATP-analog•RNA complex shows the localization of the RNA inside a tunnel formed by the two RecA-like and C-terminal domains. In the ATP-bound state this tunnel can be transformed into a groove prone for RNA binding by large rearrangements of the C-terminal domains. Several conformational changes between the ATP- and ADP-bound states explain the coupling of ATP hydrolysis to RNA translocation, mainly mediated by a β-turn of the RecA1 domain containing the newly identified RF motif. This mechanism is clearly different to those of other RNA helicases.



2007 ◽  
Vol 22 (39) ◽  
pp. 2979-2992 ◽  
Author(s):  
JIAO-KAI CHEN ◽  
ZHENG-XIN TANG ◽  
QING-DONG CHEN

The general form of the Bethe–Salpeter wave functions for bound states comprising one scalar constituent and one fermion, or two scalars is presented. Using the reduced Salpeter equation obtained, we can work out the effective nonrelativistic potentials. And one new version of reduced Bethe–Salpeter equation is proposed by extending Gross approximation.



2015 ◽  
Vol 24 (14) ◽  
pp. 1550102 ◽  
Author(s):  
Haryanto M. Siahaan

In this paper, we show the instability of a charged massive scalar field in bound states around Kerr–Sen black holes. By matching the near and far region solutions of the radial part in the corresponding Klein–Gordon equation, one can show that the frequency of bound state scalar fields contains an imaginary component which gives rise to an amplification factor for the fields. Hence, the unstable modes for a charged and massive scalar perturbation in Kerr–Sen background can be shown.



2015 ◽  
Vol 70 (4) ◽  
pp. 245-249 ◽  
Author(s):  
Hassan Hassanabadi ◽  
Antonio Soares de Castro

AbstractWith a general mixing of vector and scalar couplings in a two-dimensional world, a short-range potential is used to explore certain features of the bound states of a spinless particle. Bound-state solutions are found in terms of the Gauss hypergeometric series when the potential parameters obey a certain constraint relation limiting the dosage of a vector coupling. The appearance of the Schiff–Snyder–Weinberg effect for a strong vector coupling and a short-range potential as well as its suppression by the addition of a scalar coupling is discussed.



2020 ◽  
Vol 35 (25) ◽  
pp. 2075002
Author(s):  
Francisco M. Fernández

We analyze the results obtained from a model consisting of the interaction between the electric quadrupole moment of a moving particle and an electric field. We argue that the system does not support bound states because the motion along the [Formula: see text] axis is unbounded. It is shown that the author obtains a wrong bound-state spectrum for the motion in the [Formula: see text] plane and that the existence of allowed cyclotron frequencies is an artifact of the approach.



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