Abstract
Leucine Rich Repeat (LRR) domains, are present in hundreds of thousands of proteins across all kingdoms of life and are typically involved in protein-protein interactions and ligand recognition. LRR domains are classified into eight classes and when examined in three dimensions seven, of them form curved solenoid-like super-helices, also described as toruses, with a beta sheet on the concave (inside) and stacked alpha-helices on the convex (outside) of the torus. Here we present an overview of the least characterized 8th class of LRR proteins, the TpLRR-like LRRs, named after the Treponema pallidum protein Tp0225. Proteins from the TpLRR class differ from the proteins in all other known LRR classes by having a flipped curvature, with the beta sheet on the convex side of the torus and irregular secondary structure instead of helices on the opposite, now concave site. TpLRR proteins also present highly divergent sequence pattern of individual repeats and can associate with specific types of additional domains. Several of the characterized proteins from this class, specifically the BspA-like proteins, were found in human bacterial and protozoan pathogens, playing an important role in the interactions between the pathogens and the host immune system. In this paper we surveyed all existing experimental structures and selected AlphaFold models of the best-known proteins containing this class of LRR repeats, analyzing the relation between the pattern of conserved residues, specific structural features and functions of these proteins.