Leucine Rich Repeat Proteins: Sequences, Mutations, Structures, and Diseases

• Published in: Protein and peptide letters
• Main Authors: Matsushima, Norio, Takatsuka, Shintaro, Miyashita, Hiroki, Kretsinger, Robert H
• Format: Journal Article
• Language: English
• Published: Netherlands 01.01.2019
• Subjects: diseases; aggregation; amino acid preference; mutations; misfolding; Leucine rich repeat protein
• ISSN: 1875-5305
• DOI: 10.2174/0929866526666181208170027

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.