Norio Matsushima*, Shintaro Takatsuka, Hiroki Miyashita and Robert H. Kretsinger Pages 108 - 131 ( 24 )
Mutations in the genes encoding Leucine Rich Repeat (LRR) containing proteins are associated with over sixty human diseases; these include high myopia, mitochondrial encephalomyopathy, and Crohn’s disease. These mutations occur frequently within the LRR domains and within the regions that shield the hydrophobic core of the LRR domain. The amino acid sequences of fifty-five LRR proteins have been published. They include Nod-Like Receptors (NLRs) such as NLRP1, NLRP3, NLRP14, and Nod-2, Small Leucine Rich Repeat Proteoglycans (SLRPs) such as keratocan, lumican, fibromodulin, PRELP, biglycan, and nyctalopin, and F-box/LRR-repeat proteins such as FBXL2, FBXL4, and FBXL12. For example, 363 missense mutations have been identified. Replacement of arginine, proline, or cysteine by another amino acid, or the reverse, is frequently observed. The diverse effects of the mutations are discussed based on the known structures of LRR proteins. These mutations influence protein folding, aggregation, oligomerization, stability, protein-ligand interactions, disulfide bond formation, and glycosylation. Most of the mutations cause loss of function and a few, gain of function.
Leucine rich repeat protein, mutations, diseases, amino acid preference, aggregation, misfolding, protein-ligand interactions.
Center for Medical Education, Sapporo Medical University, Sapporo 060-8556, Center for Medical Education, Sapporo Medical University, Sapporo 060-8556, Institute of Tandem Repeats, Noboribetsu 059-0464, Department of Biology, University of Virginia, Charlottesville, VA 22904