The Small β-Barrel Domain: A Survey-Based Structural Analysis

The small β-barrel (SBB) is an ancient protein structural domain characterized by extremes: it features a broad range of structural varieties, a deeply intricate evolutionary history, and it is associated with a bewildering array of cellular pathways. Here, we present a thorough, survey-based analysis of the structural properties of SBBs. We first consider the defining properties of the SBB, including various systems of nomenclature used to describe it, and we introduce the unifying concept of an “urfold.” To begin elucidating how vast functional diversity can be achieved by a relatively simple domain, we explore the anatomy of the SBB and its representative structural variants. Many SBB proteins assemble into cyclic oligomers as the biologically functional units; these oligomers often bind RNA, and typically exhibit great quaternary structural plasticity (homomeric and heteromeric rings, variable subunit stoichiometries, etc.). We conclude with three themes that emerge from the rich structure ↔ function versatility of the SBB. [Display omitted] Youkharibache et al. describe small β-barrel (SBB) structures, which are adopted by a vast range of protein sequences. SBBs feature many intriguing properties, including a conserved three-dimensional architecture (despite differing β-topologies), extensive modularity and structural variation, multiple assembly states, and a deep diversity of RNA-, DNA-, and protein-related functions.