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Structural and evolutionary insights into astacin metallopeptidases

The astacins are a family of metallopeptidases (MPs) that has been extensively described from animals. They are multidomain extracellular proteins, which have a conserved core architecture encompassing a signal peptide for secretion, a prodomain or prosegment and a zinc-dependent catalytic domain (C...

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Autores principales: Gomis-Rüth, F. Xavier, Stöcker, Walter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9848320/
https://www.ncbi.nlm.nih.gov/pubmed/36685277
http://dx.doi.org/10.3389/fmolb.2022.1080836
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author Gomis-Rüth, F. Xavier
Stöcker, Walter
author_facet Gomis-Rüth, F. Xavier
Stöcker, Walter
author_sort Gomis-Rüth, F. Xavier
collection PubMed
description The astacins are a family of metallopeptidases (MPs) that has been extensively described from animals. They are multidomain extracellular proteins, which have a conserved core architecture encompassing a signal peptide for secretion, a prodomain or prosegment and a zinc-dependent catalytic domain (CD). This constellation is found in the archetypal name-giving digestive enzyme astacin from the European crayfish Astacus astacus. Astacin catalytic domains span ∼200 residues and consist of two subdomains that flank an extended active-site cleft. They share several structural elements including a long zinc-binding consensus sequence (HEXXHXXGXXH) immediately followed by an EXXRXDRD motif, which features a family-specific glutamate. In addition, a downstream SIMHY-motif encompasses a “Met-turn” methionine and a zinc-binding tyrosine. The overall architecture and some structural features of astacin catalytic domains match those of other more distantly related MPs, which together constitute the metzincin clan of metallopeptidases. We further analysed the structures of PRO-, MAM, TRAF, CUB and EGF-like domains, and described their essential molecular determinants. In addition, we investigated the distribution of astacins across kingdoms and their phylogenetic origin. Through extensive sequence searches we found astacin CDs in > 25,000 sequences down the tree of life from humans beyond Metazoa, including Choanoflagellata, Filasterea and Ichtyosporea. We also found < 400 sequences scattered across non-holozoan eukaryotes including some fungi and one virus, as well as in selected taxa of archaea and bacteria that are pathogens or colonizers of animal hosts, but not in plants. Overall, we propose that astacins originate in the root of Holozoa consistent with Darwinian descent and that the latter genes might be the result of horizontal gene transfer from holozoan donors.
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spelling pubmed-98483202023-01-19 Structural and evolutionary insights into astacin metallopeptidases Gomis-Rüth, F. Xavier Stöcker, Walter Front Mol Biosci Molecular Biosciences The astacins are a family of metallopeptidases (MPs) that has been extensively described from animals. They are multidomain extracellular proteins, which have a conserved core architecture encompassing a signal peptide for secretion, a prodomain or prosegment and a zinc-dependent catalytic domain (CD). This constellation is found in the archetypal name-giving digestive enzyme astacin from the European crayfish Astacus astacus. Astacin catalytic domains span ∼200 residues and consist of two subdomains that flank an extended active-site cleft. They share several structural elements including a long zinc-binding consensus sequence (HEXXHXXGXXH) immediately followed by an EXXRXDRD motif, which features a family-specific glutamate. In addition, a downstream SIMHY-motif encompasses a “Met-turn” methionine and a zinc-binding tyrosine. The overall architecture and some structural features of astacin catalytic domains match those of other more distantly related MPs, which together constitute the metzincin clan of metallopeptidases. We further analysed the structures of PRO-, MAM, TRAF, CUB and EGF-like domains, and described their essential molecular determinants. In addition, we investigated the distribution of astacins across kingdoms and their phylogenetic origin. Through extensive sequence searches we found astacin CDs in > 25,000 sequences down the tree of life from humans beyond Metazoa, including Choanoflagellata, Filasterea and Ichtyosporea. We also found < 400 sequences scattered across non-holozoan eukaryotes including some fungi and one virus, as well as in selected taxa of archaea and bacteria that are pathogens or colonizers of animal hosts, but not in plants. Overall, we propose that astacins originate in the root of Holozoa consistent with Darwinian descent and that the latter genes might be the result of horizontal gene transfer from holozoan donors. Frontiers Media S.A. 2023-01-04 /pmc/articles/PMC9848320/ /pubmed/36685277 http://dx.doi.org/10.3389/fmolb.2022.1080836 Text en Copyright © 2023 Gomis-Rüth and Stöcker. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Gomis-Rüth, F. Xavier
Stöcker, Walter
Structural and evolutionary insights into astacin metallopeptidases
title Structural and evolutionary insights into astacin metallopeptidases
title_full Structural and evolutionary insights into astacin metallopeptidases
title_fullStr Structural and evolutionary insights into astacin metallopeptidases
title_full_unstemmed Structural and evolutionary insights into astacin metallopeptidases
title_short Structural and evolutionary insights into astacin metallopeptidases
title_sort structural and evolutionary insights into astacin metallopeptidases
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9848320/
https://www.ncbi.nlm.nih.gov/pubmed/36685277
http://dx.doi.org/10.3389/fmolb.2022.1080836
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