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Evolutionary conservation of intrinsically unstructured regions in slit-diaphragm proteins
Vertebrate kidneys contribute to homeostasis by regulating electrolyte, acid-base balance, removing toxic metabolites from blood, and preventing protein loss into the urine. Glomerular podocytes constitute the blood-urine barrier, and podocyte slit-diaphragm (SD), a modified tight junction, contribu...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294545/ https://www.ncbi.nlm.nih.gov/pubmed/34288970 http://dx.doi.org/10.1371/journal.pone.0254917 |
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author | Mulukala, Sandeep K. N. Kambhampati, Vaishnavi Qadri, Abrar H. Pasupulati, Anil K. |
author_facet | Mulukala, Sandeep K. N. Kambhampati, Vaishnavi Qadri, Abrar H. Pasupulati, Anil K. |
author_sort | Mulukala, Sandeep K. N. |
collection | PubMed |
description | Vertebrate kidneys contribute to homeostasis by regulating electrolyte, acid-base balance, removing toxic metabolites from blood, and preventing protein loss into the urine. Glomerular podocytes constitute the blood-urine barrier, and podocyte slit-diaphragm (SD), a modified tight junction, contributes to the glomerular permselectivity. Nephrin, KIRREL1, podocin, CD2AP, and TRPC6 are crucial members of the SD that interact with each other and contribute to the SD’s structural and functional integrity. This study analyzed the distribution of these five essential SD proteins across the organisms for which the genome sequence is available. We found a diverse distribution of nephrin and KIRREL1 ranging from nematodes to higher vertebrates, whereas podocin, CD2AP, and TRPC6 are restricted to the vertebrates. Among invertebrates, nephrin and its orthologs consist of more immunoglobulin-3 domains, whereas in the vertebrates, CD80-like C2-set domains are predominant. In the case of KIRREL1 and its orthologs, more Ig domains were observed in invertebrates than vertebrates. Src Homology-3 (SH3) domain of CD2AP and SPFH domain of podocin are highly conserved among vertebrates. TRPC6 and its orthologs had conserved ankyrin repeats, TRP, and ion transport domains, except Chondrichthyes and Echinodermata, which do not possess the ankyrin repeats. Intrinsically unstructured regions (IURs) are conserved across the SD orthologs, suggesting IURs importance in the protein complexes that constitute the slit-diaphragm. For the first time, a study reports the evolutionary insights of vertebrate SD proteins and their invertebrate orthologs. |
format | Online Article Text |
id | pubmed-8294545 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-82945452021-07-31 Evolutionary conservation of intrinsically unstructured regions in slit-diaphragm proteins Mulukala, Sandeep K. N. Kambhampati, Vaishnavi Qadri, Abrar H. Pasupulati, Anil K. PLoS One Research Article Vertebrate kidneys contribute to homeostasis by regulating electrolyte, acid-base balance, removing toxic metabolites from blood, and preventing protein loss into the urine. Glomerular podocytes constitute the blood-urine barrier, and podocyte slit-diaphragm (SD), a modified tight junction, contributes to the glomerular permselectivity. Nephrin, KIRREL1, podocin, CD2AP, and TRPC6 are crucial members of the SD that interact with each other and contribute to the SD’s structural and functional integrity. This study analyzed the distribution of these five essential SD proteins across the organisms for which the genome sequence is available. We found a diverse distribution of nephrin and KIRREL1 ranging from nematodes to higher vertebrates, whereas podocin, CD2AP, and TRPC6 are restricted to the vertebrates. Among invertebrates, nephrin and its orthologs consist of more immunoglobulin-3 domains, whereas in the vertebrates, CD80-like C2-set domains are predominant. In the case of KIRREL1 and its orthologs, more Ig domains were observed in invertebrates than vertebrates. Src Homology-3 (SH3) domain of CD2AP and SPFH domain of podocin are highly conserved among vertebrates. TRPC6 and its orthologs had conserved ankyrin repeats, TRP, and ion transport domains, except Chondrichthyes and Echinodermata, which do not possess the ankyrin repeats. Intrinsically unstructured regions (IURs) are conserved across the SD orthologs, suggesting IURs importance in the protein complexes that constitute the slit-diaphragm. For the first time, a study reports the evolutionary insights of vertebrate SD proteins and their invertebrate orthologs. Public Library of Science 2021-07-21 /pmc/articles/PMC8294545/ /pubmed/34288970 http://dx.doi.org/10.1371/journal.pone.0254917 Text en © 2021 Mulukala et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Mulukala, Sandeep K. N. Kambhampati, Vaishnavi Qadri, Abrar H. Pasupulati, Anil K. Evolutionary conservation of intrinsically unstructured regions in slit-diaphragm proteins |
title | Evolutionary conservation of intrinsically unstructured regions in slit-diaphragm proteins |
title_full | Evolutionary conservation of intrinsically unstructured regions in slit-diaphragm proteins |
title_fullStr | Evolutionary conservation of intrinsically unstructured regions in slit-diaphragm proteins |
title_full_unstemmed | Evolutionary conservation of intrinsically unstructured regions in slit-diaphragm proteins |
title_short | Evolutionary conservation of intrinsically unstructured regions in slit-diaphragm proteins |
title_sort | evolutionary conservation of intrinsically unstructured regions in slit-diaphragm proteins |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294545/ https://www.ncbi.nlm.nih.gov/pubmed/34288970 http://dx.doi.org/10.1371/journal.pone.0254917 |
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