Configuration Interaction of Hydropathic Waves Enables Ubiquitin Functionality [PDF]
Ubiquitin, discovered less than 50 years ago, tags thousands of diseased proteins for destruction. It is small (only 76 amino acids), and is found unchanged in mammals, birds, fish and even worms. Key features of its functionality are identified here using critical point thermodynamic scaling theory.
arxiv
The Ubiquitin Binding Domain ZnF UBP Recognizes the C-Terminal Diglycine Motif of Unanchored Ubiquitin [PDF]
SummaryUbiquitin binding proteins regulate the stability, function, and/or localization of ubiquitinated proteins. Here we report the crystal structures of the zinc-finger ubiquitin binding domain (ZnF UBP) from the deubiquitinating enzyme isopeptidase T
Cheng, Xiaodong+5 more
core +1 more source
Ubiquitination of transcription factors in cancer: unveiling therapeutic potential
In cancer, dysregulated ubiquitination of transcription factors contributes to the uncontrolled growth and survival characteristics of tumors. Tumor suppressors are degraded by aberrant ubiquitination, or oncogenic transcription factors gain stability through ubiquitination, thereby promoting tumorigenesis.
Dongha Kim, Hye Jin Nam, Sung Hee Baek
wiley +1 more source
Proteins in a shear flow [PDF]
The conformational dynamics of a single protein molecule in a shear flow is investigated using Brownian dynamics simulations. A structure-based coarse grained model of a protein is used. We consider two proteins, ubiquitin and integrin, and find that at moderate shear rates they unfold through a sequence of metastable states - a pattern which is ...
arxiv +1 more source
Targeted protein degradation in oncology: novel therapeutic opportunity for solid tumours?
Current anticancer therapies are limited by the occurrence of resistance and undruggability of most proteins. Targeted protein degraders are novel, promising agents that trigger the selective degradation of previously undruggable proteins through the recruitment of the ubiquitin–proteasome machinery. Their mechanism of action raises exciting challenges,
Noé Herbel, Sophie Postel‐Vinay
wiley +1 more source
A mathematical model of p62-ubiquitin aggregates in autophagy [PDF]
Aggregation of ubiquitinated cargo by oligomers of the protein p62 is an important preparatory step in cellular autophagy. In this work a mathematical model for the dynamics of these heterogeneous aggregates in the form of a system of ordinary differential equations is derived and analyzed. Three different parameter regimes are identified, where either
arxiv
Interface of the polarizable continuum model of solvation with semi-empirical methods in the GAMESS program [PDF]
An interface between semi-empirical methods and the polarized continuum model (PCM) of solvation successfully implemented into GAMESS following the approach by Chudinov et al (Chem. Phys. 1992, 160, 41). The interface includes energy gradients and is parallelized.
arxiv +1 more source
Nuclear prothymosin α inhibits epithelial‐mesenchymal transition (EMT) in lung cancer by increasing Smad7 acetylation and competing with Smad2 for binding to SNAI1, TWIST1, and ZEB1 promoters. In early‐stage cancer, ProT suppresses TGF‐β‐induced EMT, while its loss in the nucleus in late‐stage cancer leads to enhanced EMT and poor prognosis.
Liyun Chen+12 more
wiley +1 more source
Energy landscape of ubiquitin modulated by periodic forces: Asymmetric protein stability and shifts in unfolding pathways [PDF]
Biological forces govern essential cellular and molecular processes in all living organisms. Many cellular forces, e.g. those generated in cyclic conformational changes of biological machines, have repetitive components. However, little is known about how proteins process repetitive mechanical stresses.
arxiv
Long-time behaviour of a model for p62-ubiquitin aggregation in cellular autophagy [PDF]
The qualitative behavior of a recently formulated ODE model for the dynamics of heterogenous aggregates is analyzed. Aggregates contain two types of particles, oligomers and cross-linkers. The motivation is a preparatory step of cellular autophagy, the aggregation of oligomers of the protein p62 in the presence of ubiquitin cross-linkers. A combination
arxiv