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CPR-C4 is a highly conserved novel protease from the Candidate Phyla Radiation with remote structural homology to human vasohibins

The Candidate Phyla Radiation is a recently uncovered and vast expansion of the bacterial domain of life, made up of largely uncharacterized phyla that lack isolated representatives. This unexplored territory of genetic diversity presents an abundance of novel proteins with potential applications in...

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Autores principales: Cornish, Katy A.S., Lange, Joanna, Aevarsson, Arnthór, Pohl, Ehmke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108980/
https://www.ncbi.nlm.nih.gov/pubmed/35405098
http://dx.doi.org/10.1016/j.jbc.2022.101919
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author Cornish, Katy A.S.
Lange, Joanna
Aevarsson, Arnthór
Pohl, Ehmke
author_facet Cornish, Katy A.S.
Lange, Joanna
Aevarsson, Arnthór
Pohl, Ehmke
author_sort Cornish, Katy A.S.
collection PubMed
description The Candidate Phyla Radiation is a recently uncovered and vast expansion of the bacterial domain of life, made up of largely uncharacterized phyla that lack isolated representatives. This unexplored territory of genetic diversity presents an abundance of novel proteins with potential applications in the life-science sectors. Here, we present the structural and functional elucidation of CPR-C4, a hypothetical protein from the genome of a thermophilic Candidate Phyla Radiation organism, identified through metagenomic sequencing. Our analyses revealed that CPR-C4 is a member of a family of highly conserved proteins within the Candidate Phyla Radiation. The function of CPR-C4 as a cysteine protease was predicted through remote structural similarity to the Homo sapiens vasohibins and subsequently confirmed experimentally with fluorescence-based activity assays. Furthermore, detailed structural and sequence alignment analysis enabled identification of a noncanonical cysteine-histidine-leucine(carbonyl) catalytic triad. The unexpected structural and functional similarities between CPR-C4 and the human vasohibins suggest an evolutionary relationship undetectable at the sequence level alone.
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spelling pubmed-91089802022-05-20 CPR-C4 is a highly conserved novel protease from the Candidate Phyla Radiation with remote structural homology to human vasohibins Cornish, Katy A.S. Lange, Joanna Aevarsson, Arnthór Pohl, Ehmke J Biol Chem Research Article The Candidate Phyla Radiation is a recently uncovered and vast expansion of the bacterial domain of life, made up of largely uncharacterized phyla that lack isolated representatives. This unexplored territory of genetic diversity presents an abundance of novel proteins with potential applications in the life-science sectors. Here, we present the structural and functional elucidation of CPR-C4, a hypothetical protein from the genome of a thermophilic Candidate Phyla Radiation organism, identified through metagenomic sequencing. Our analyses revealed that CPR-C4 is a member of a family of highly conserved proteins within the Candidate Phyla Radiation. The function of CPR-C4 as a cysteine protease was predicted through remote structural similarity to the Homo sapiens vasohibins and subsequently confirmed experimentally with fluorescence-based activity assays. Furthermore, detailed structural and sequence alignment analysis enabled identification of a noncanonical cysteine-histidine-leucine(carbonyl) catalytic triad. The unexpected structural and functional similarities between CPR-C4 and the human vasohibins suggest an evolutionary relationship undetectable at the sequence level alone. American Society for Biochemistry and Molecular Biology 2022-04-08 /pmc/articles/PMC9108980/ /pubmed/35405098 http://dx.doi.org/10.1016/j.jbc.2022.101919 Text en Crown Copyright © 2022 Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Article
Cornish, Katy A.S.
Lange, Joanna
Aevarsson, Arnthór
Pohl, Ehmke
CPR-C4 is a highly conserved novel protease from the Candidate Phyla Radiation with remote structural homology to human vasohibins
title CPR-C4 is a highly conserved novel protease from the Candidate Phyla Radiation with remote structural homology to human vasohibins
title_full CPR-C4 is a highly conserved novel protease from the Candidate Phyla Radiation with remote structural homology to human vasohibins
title_fullStr CPR-C4 is a highly conserved novel protease from the Candidate Phyla Radiation with remote structural homology to human vasohibins
title_full_unstemmed CPR-C4 is a highly conserved novel protease from the Candidate Phyla Radiation with remote structural homology to human vasohibins
title_short CPR-C4 is a highly conserved novel protease from the Candidate Phyla Radiation with remote structural homology to human vasohibins
title_sort cpr-c4 is a highly conserved novel protease from the candidate phyla radiation with remote structural homology to human vasohibins
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108980/
https://www.ncbi.nlm.nih.gov/pubmed/35405098
http://dx.doi.org/10.1016/j.jbc.2022.101919
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