[Frontiers in Bioscience 17, 1433-1460, January 1, 2012]

The natural history of ubiquitin and ubiquitin-related domains

Alexander Maxwell Burroughs1, Lakshminarayan M. Iyer2, L Aravind2

1Omics Science Center (OSC), RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama-shi, 230-0045 Kanagawa, Japan, 2National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, United States of America


1. Abstract
2. Introduction
3. Core conserved topology, structural variation, and derivatives of the beta-GF
4. Nature classification of beta-GF domains
4.1. Basal and other 4-stranded versions of the beta-GF
4.2. The 5-stranded assemblage
5. The relative timeline of major adaptive radiations and functional transitions of the beta-GF domains
5.1. The pre-LUCA phase and inference of the ancestral function of the beta-GF
5.2. The post-LUCA phase: the prokaryotic superkingdoms
5.3. The post-LUCA phase: covalently-attached protein modifiers emerge from sulfur carriers
5.4. Emergence of other possible links between protein stability and Ubl domains in prokaryotes
5.5. The eukaryotic phase of beta-GF evolution: expansion of the ubiquitin-like domains
6. Evolutionary trends in the domain architectures of beta-GF domains
6. 1. General architectural themes in the beta-GF
6.2. Structural correlates for functional diversity in the beta-GF
7. Perspectives and general conclusions
8. Acknowledgements
9. References


The ubiquitin (Ub) system is centered on conjugation and deconjugation of Ub and Ub-like (Ubls) proteins by a system of ligases and peptidases, respectively. Ub/Ubls contain the beta-grasp fold, also found in numerous proteins with biochemically distinct roles unrelated to the conventional Ub-system. The beta-GF underwent an early radiation spawning at least seven clades prior to the divergence of extant organisms from their last universal common ancestor, first emerging in the context of translation-related RNA-interactions and subsequently exploding to occupy various functional niches. Most beta-GF diversification occurred in prokaryotes, with the Ubl clade showing dramatic expansion in the eukaryotes. Diversification of Ubl families in eukaryotes played a major role in emergence of characteristic eukaryotic cellular sub-structures and systems. Recent comparative genomics studies indicate precursors of the eukaryotic Ub-system emerged in prokaryotes. The simplest of these combine an Ubl and an E1-like enzyme in metabolic pathways. Sampylation in archaea and Urmylation in eukaryotes appear to represent recruitment of such systems as simple protein-tagging apparatuses. However, other prokaryotic systems incorporated further components and mirror the eukaryotic condition in possessing an E2, a RING-type E3 or both of these components. Additionally, prokaryotes have evolved conjugation systems independent of Ub ligases, such as the Pup system.