Protein primary structure correlates with calcium oxalate stone matrix preference.

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 charg...

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Autores principales:	Yu Tian, Matthew Tirrell, Carley Davis, Jeffrey A Wesson
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0ba1e54b271e4a1fb1da0ee01f30975a
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spelling	oai:doaj.org-article:0ba1e54b271e4a1fb1da0ee01f30975a2021-12-02T20:08:03ZProtein primary structure correlates with calcium oxalate stone matrix preference.1932-620310.1371/journal.pone.0257515https://doaj.org/article/0ba1e54b271e4a1fb1da0ee01f30975a2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0257515https://doaj.org/toc/1932-6203Despite 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.Yu TianMatthew TirrellCarley DavisJeffrey A WessonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 9, p e0257515 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yu Tian Matthew Tirrell Carley Davis Jeffrey A Wesson Protein primary structure correlates with calcium oxalate stone matrix preference.
description	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.
format	article
author	Yu Tian Matthew Tirrell Carley Davis Jeffrey A Wesson
author_facet	Yu Tian Matthew Tirrell Carley Davis Jeffrey A Wesson
author_sort	Yu Tian
title	Protein primary structure correlates with calcium oxalate stone matrix preference.
title_short	Protein primary structure correlates with calcium oxalate stone matrix preference.
title_full	Protein primary structure correlates with calcium oxalate stone matrix preference.
title_fullStr	Protein primary structure correlates with calcium oxalate stone matrix preference.
title_full_unstemmed	Protein primary structure correlates with calcium oxalate stone matrix preference.
title_sort	protein primary structure correlates with calcium oxalate stone matrix preference.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/0ba1e54b271e4a1fb1da0ee01f30975a
work_keys_str_mv	AT yutian proteinprimarystructurecorrelateswithcalciumoxalatestonematrixpreference AT matthewtirrell proteinprimarystructurecorrelateswithcalciumoxalatestonematrixpreference AT carleydavis proteinprimarystructurecorrelateswithcalciumoxalatestonematrixpreference AT jeffreyawesson proteinprimarystructurecorrelateswithcalciumoxalatestonematrixpreference
_version_	1718375223816880128

Protein primary structure correlates with calcium oxalate stone matrix preference.

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