Why Ubiquitin Has Not Evolved

Abstract

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, indicating that ubiquitin is perfect. Key features of its functionality are identified here using critical point thermodynamic scaling theory. These include synchronized pivots and hinges, a stabilizing central pivot, and Fano interference between first- and second-order elements of correlated long-range (allosteric) globular surface shape transitions. Comparison with its closest relative, 76 amino acid Nedd8, shows that the latter lacks all these features. A cracked elastic network model is proposed for the common target shared by many diseased proteins.

Retroelement-Linked H3K4me1 Histone Tags Uncover Regulatory Evolution Trends of Gene Enhancers and Feature Quickly Evolving Molecular Processes in Human Physiology

“…On the other hand, the conservative (RRE-deficient) molecular processes identified here are also in some aspects congruent with those identified previously by TFBS analysis [21] and with some general evolutionary trends established by other methods. For example, the “Protein ubiquitination and degradation” group is one of the most conservative core intracellular processes [68]. Similarly, the “General signaling pathways” group was found as a group with relatively low regulatory evolution, also in the RetroSpect TFBS analysis [21].…”

Ubiquitin System

“…In this regard, Beclin 1, a key regulator of autophagy, is modified by distinct types of ubiquitin chains to control autophagy pathways, including autophagosome formation, which is reviewed by Boutouja et al [ 16 ]. Ubiquitin is an evolutionarily-conserved protein, the functionality of which was explained in the paper of Allan and Phillips through their analysis using thermodynamic scaling [ 17 ]. Thus, polyubiquitin chains can be formed through one of the seven lysine residues or the first methionine residue of ubiquitin in a variety of species.…”

Más Allá de La Filogenética: Evolución Darwiniana de La Actina

“…de cadenas β cerca de los terminales n y c en la escala de tiempo de microsegundos a milisegundos [18] . La función de etiquetado de la Ub es consistente con su perfil hidrofóbico y sugiere un modelo de red elástica agrietada para el blanco común compartido por muchas proteínas enfermas [19] . La Uba (E1) es 14 veces más grande que la Uba y también ha evolucionado muy poco, pero esa pequeña evolución rastrea la nivelación de los extremos hidrofóbicos del parámetro Ψ (aa,W*) [20] .…”