116 research outputs found
KRAS Ubiquitination at Lysine 104 Retains Exchange Factor Regulation by Dynamically Modulating the Conformation of the Interface
RAS proteins function as highly regulated molecular switches that control cellular growth. In addition to regulatory proteins, RAS undergoes a number of posttranslational modifications (PTMs) that regulate its activity. Lysine 104, a hot spot for multiple PTMs, is a highly conserved residue that forms key interactions that stabilize the RAS helix-2(H2)/helix-3(H3) interface. Mutation at 104 attenuates interaction with guanine nucleotide exchange factors (GEFs), whereas ubiquitination at lysine 104 retains GEF regulation. To elucidate how ubiquitination modulates RAS function, we generated monoubiquitinated KRAS at 104 using chemical biology approaches and conducted biochemical, NMR, and computational analyses. We find that ubiquitination promotes a new dynamic interaction network and alters RAS conformational dynamics to retain GEF function. These findings reveal a mechanism by which ubiquitination can regulate protein function
T2 phase site occupancies in the Cr--Si--B system: a combined synchroton-XRD/first-principles study
Boron and Silicon site occupancies of the T2 phase in the Cr-Si-B system were
investigated experimentally and by first-principles electronic-structure
calculations within the scope of the Density Functional Theory (DFT). A sample
with nominal composition CrBSi was arc-melted under
argon, encapsulated in a quartz-tube and heat-treated at 1400{\deg}C for 96
hours. It was then analyzed using Scanning Electron Microscopy (SEM) and X-Ray
Diffractometry (XRD) with synchrotron radiation. An excellent agreement was
obtained between experiments and theoretical calculations, revealing that Si
occupies preferably the sublattice of the structure due to the presence of
weak B bonds, making the site preferences a key factor for its stabilization.
The results of this work provide important information to support a better
description of this phase in alloys with Si and B, since T2 phases are known to
occur in many important Transition Metal-Si-B ternary systems, such as
Nb/Mo/W/Ta/V-Si-B
A pyrazine bis-adduct of a binuclear rhodium(II) carboxylate containing 3,4,5-triethoxybenzoate as the equatorial ligand
The title compound, tetrakis(μ-3,4,5-triethoxyÂbenzoato-κ2O:O′)ÂbisÂ[(pyrazine-κN)Ârhodium(II)](Rh—Rh), [Rh2(C13H17O5)4(C4H4N2)2], crystallizes on an inversion centre in the triclinic space group P ‾1. The equatorial carboxylÂate ligands bridge the two RhII atoms, giving a binuclear lantern-like structure. The pyrazine molÂecules occupy the two axial coordination sites. The phenyl rings are tilted by ca 10° with respect to the attached carboxylÂate groups. The pyrazine planes have a torsion angle of ca 19° around the Rh—N bond with respect to the plane of the nearer carboxylÂate group and are not coplanar with the Rh—Rh bond.Instituto de FÃsica La Plat
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