Configuration interaction of hydropathic waves enables ubiquitin functionality

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. Key features of its functionality are identified here using critical point thermodynamic scaling theory. These include Fano interference between first-and second-order elements of globular surface shape transitions. Comparison with its closest relative, 76 amino acid Nedd8, shows that the latter lacks these features. A cracked elastic network model is proposed for the common target shared by many diseased proteins.Between the 1960s and 1980s, most life scientists focused their attention on protein creation by DNA and the translation of its coded information. Protein degradation was a neglected area, considered to be a nonspecific, dead-end process. Although it was known that proteins do turn over, the large extent and high specificity of the process, whereby distinct proteins have halflives that range from a few minutes to several days, was not appreciated. The discovery of the complex cascade of the ubiquitin pathway revolutionized the field [1]. Today attention continues to be focused on DNA-based personalized medicine, but the very size of DNA makes this a challenging prospect.The extent and especially the depth of our understanding of individual proteins continue to grow in unexpected ways. Ubiquitin, discovered as the protein that targets other proteins for degradation [2], is the subject of multiple international conferences annually. Here we apply theoretical tools that show that ubiquitin has something very special in combination with

Evolution of the ubiquitin-activating enzyme Uba1 (E1)

“…Because of its universality, Ub is a valuable proving ground for universal biophysical theories discussing protein amino acid sequences, structure and function [3]. Indeed key features of Ub functionality (hydropathic waves) were identified using critical point thermodynamic scaling theory [4]. The general biochemical logistics of Ub activation, conjugation and ligation are orchestrated sequentially by the Ub conjugation cascade of E1, E2 and E3 enzymes.…”

“…As before [3,4], all calculations are based on thermodynamically first-and second-order hydropathic Ψ(amino acid) scales [6,7], linearly scaled to a common center and a common range for each of the 20 amino acids. These are then converted to a triangular matrix Ψ(aa,W), where W is the length of a sliding window centered on each amino acid site.…”