Protein primary structure correlates with calcium oxalate stone matrix preference. PLoS One 2021;16(9):e0257515
Date
09/24/2021Pubmed ID
34555074Pubmed Central ID
PMC8459966DOI
10.1371/journal.pone.0257515Scopus ID
2-s2.0-85115750217 (requires institutional sign-in at Scopus site) 6 CitationsAbstract
Despite the apparent importance of matrix proteins in calcium oxalate kidney stone formation, the complexity of the protein mixture continues to elude explanation. Based on a series of experiments, we have proposed a model where protein aggregates formed from a mixture containing both strongly charged polyanions and strongly charged polycations could initiate calcium oxalate crystal formation and crystal aggregation to create a stone. These protein aggregates also preferentially adsorb many weakly charged proteins from the urine to create a complex protein mixture that mimics the protein distributions observed in patient samples. To verify essential details of this model and identify an explanation for phase selectivity observed in weakly charged proteins, we have examined primary structures of major proteins preferring either the matrix phase or the urine phase for their contents of aspartate, glutamate, lysine and arginine; amino acids that would represent fixed charges at normal urine pH of 6-7. We verified enrichment in stone matrix of proteins with a large number of charged residues exhibiting extreme isoelectric points, both low (pI<5) and high (pI>9). We found that the many proteins with intermediate isoelectric points exhibiting preference for stone matrix contained a smaller number of charge residues, though still more total charges than the intermediate isoelectric point proteins preferring the urine phase. While other sources of charge have yet to be considered, protein preference for stone matrix appears to correlate with high total charge content.
Author List
Tian Y, Tirrell M, Davis C, Wesson JAAuthors
Carley Davis MD Professor in the Urologic Surgery department at Medical College of WisconsinJeffrey A. Wesson MD, PhD Professor in the Medicine department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Calcium OxalateCrystallization
Kidney Calculi
Proteins
