Leucine-Rich Repeats (LRR) are tandem arrays of 20 to 30 amino acid residues that are widespread structural motifs present in more than 6000 proteins across species ranging from viruses to eukaryotes. The major role of LRR domains in proteins is to serve as a structural framework for the interactions with other proteins or non-proteinaceous ligands. Approximately 400 human LRR-containing proteins involve in various physiological processes including hormone response (FSHR, TSHR, LHR), immune response (TLR, NOD, NALP, NAIP and CD14), neurogenesis and synaptogenesis (NTRK, SLIT, NGL, LRRTM, SALM, LGI), protein degradation (F-box protein), cell differentiation (LGR5), autophagy (LRRK) and many others. In addition, mutations or polymorphisms in LRR-containing proteins have been implicated in numerous human diseases such as schizophrenia, Parkinson’s disease, cancer, Crohn’s disease, congenital blindness, polycystic kidney disease and ovarian dysgenesis. A number of LRR-containing proteins have been extensively studied due to their significance in physiological and pathological processes, but still a certain type of LRR-containing proteins remains largely uncharacterized.
Our research group is undertaking innovative research to discover the novel binding targets of uncharacterized LRR-containing proteins and their cellular signaling network. These novel binding partners for uncharacterized LRR-containing proteins as well as the supramolecular signaling complexes will be the key targets for our structural research. We hope that our challenging approach will open a groundbreaking research field with the goal of expanding our understanding on the physiological and pathological roles of uncharacterized LRR-containing proteins. Moreover, the mechanistic insights from our integrative study on structure and function of various LRR-containing proteins can be also translated clinically in the form of diagnostic bio-markers as well as protein therapeutics.