The VCBS superfamily, a diverse group of β-propellers that includes tachylectin and integrins

{beta}-Propellers are found in great variety across all kingdoms of life. They assume many cellular roles, primarily as scaffolds for macromolecular interactions and catalysis. Despite their diversity, most {beta}-propeller families clearly originated by amplification from the same ancient peptide - the {beta}-propeller blade. In cluster analyses, {beta}-propellers of the WD40 superfamily always formed the largest group, to which some important families, such as the -integrin, Asp-box, and glycoside hydrolase {beta}-propellers connected weakly. Motivated by the dramatic growth of sequence databases we revisited these connections, with a special focus on VCBS-like {beta}-propellers, which have not been analysed for their evolutionary relationships so far. We found that they form a supercluster with integrin-like {beta}-propellers and tachylectins, clearly delimited from the superclusters formed by WD40 and Asp-Box {beta}-propeller. Connections between the three superclusters are made mainly through PQQ-like {beta}-propeller. Our results present a new, greatly expanded view of the {beta}-propeller classification landscape.