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Comparative Structure Analysis of the Multi-Domain, Cell Envelope Proteases of Lactic Acid Bacteria

Lactic acid bacteria (LAB) have an extracellular proteolytic system that includes a multi-domain, cell envelope protease (CEP) with a subtilisin homologous protease domain. These CEPs have different proteolytic activities despite having similar protein sequences. Structural characterization has prev...

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Autores principales: Christensen, Lise Friis, Høie, Magnus Haraldson, Bang-Berthelsen, Claus Heiner, Marcatili, Paolo, Hansen, Egon Bech
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10535647/
https://www.ncbi.nlm.nih.gov/pubmed/37764099
http://dx.doi.org/10.3390/microorganisms11092256
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author Christensen, Lise Friis
Høie, Magnus Haraldson
Bang-Berthelsen, Claus Heiner
Marcatili, Paolo
Hansen, Egon Bech
author_facet Christensen, Lise Friis
Høie, Magnus Haraldson
Bang-Berthelsen, Claus Heiner
Marcatili, Paolo
Hansen, Egon Bech
author_sort Christensen, Lise Friis
collection PubMed
description Lactic acid bacteria (LAB) have an extracellular proteolytic system that includes a multi-domain, cell envelope protease (CEP) with a subtilisin homologous protease domain. These CEPs have different proteolytic activities despite having similar protein sequences. Structural characterization has previously been limited to CEP homologs of dairy- and human-derived LAB strains, excluding CEPs of plant-derived LAB strains. CEP structures are a challenge to determine experimentally due to their large size and attachment to the cell envelope. This study aims to clarify the prevalence and structural diversity of CEPs by using the structure prediction software AlphaFold 2. Domain boundaries are clarified based on a comparative analysis of 21 three-dimensional structures, revealing novel domain architectures of CEP homologs that are not necessarily restricted to specific LAB species or ecological niches. The C-terminal flanking region of the protease domain is divided into fibronectin type-III-like domains with various structural traits. The analysis also emphasizes the existence of two distinct domains for cell envelope attachment that are preceded by an intrinsically disordered cell wall spanning domain. The domain variants and their combinations provide CEPs with different stability, proteolytic activity, and potentially adhesive properties, making CEPs targets for steering proteolytic activity with relevance for both food development and human health.
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spelling pubmed-105356472023-09-29 Comparative Structure Analysis of the Multi-Domain, Cell Envelope Proteases of Lactic Acid Bacteria Christensen, Lise Friis Høie, Magnus Haraldson Bang-Berthelsen, Claus Heiner Marcatili, Paolo Hansen, Egon Bech Microorganisms Article Lactic acid bacteria (LAB) have an extracellular proteolytic system that includes a multi-domain, cell envelope protease (CEP) with a subtilisin homologous protease domain. These CEPs have different proteolytic activities despite having similar protein sequences. Structural characterization has previously been limited to CEP homologs of dairy- and human-derived LAB strains, excluding CEPs of plant-derived LAB strains. CEP structures are a challenge to determine experimentally due to their large size and attachment to the cell envelope. This study aims to clarify the prevalence and structural diversity of CEPs by using the structure prediction software AlphaFold 2. Domain boundaries are clarified based on a comparative analysis of 21 three-dimensional structures, revealing novel domain architectures of CEP homologs that are not necessarily restricted to specific LAB species or ecological niches. The C-terminal flanking region of the protease domain is divided into fibronectin type-III-like domains with various structural traits. The analysis also emphasizes the existence of two distinct domains for cell envelope attachment that are preceded by an intrinsically disordered cell wall spanning domain. The domain variants and their combinations provide CEPs with different stability, proteolytic activity, and potentially adhesive properties, making CEPs targets for steering proteolytic activity with relevance for both food development and human health. MDPI 2023-09-08 /pmc/articles/PMC10535647/ /pubmed/37764099 http://dx.doi.org/10.3390/microorganisms11092256 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Christensen, Lise Friis
Høie, Magnus Haraldson
Bang-Berthelsen, Claus Heiner
Marcatili, Paolo
Hansen, Egon Bech
Comparative Structure Analysis of the Multi-Domain, Cell Envelope Proteases of Lactic Acid Bacteria
title Comparative Structure Analysis of the Multi-Domain, Cell Envelope Proteases of Lactic Acid Bacteria
title_full Comparative Structure Analysis of the Multi-Domain, Cell Envelope Proteases of Lactic Acid Bacteria
title_fullStr Comparative Structure Analysis of the Multi-Domain, Cell Envelope Proteases of Lactic Acid Bacteria
title_full_unstemmed Comparative Structure Analysis of the Multi-Domain, Cell Envelope Proteases of Lactic Acid Bacteria
title_short Comparative Structure Analysis of the Multi-Domain, Cell Envelope Proteases of Lactic Acid Bacteria
title_sort comparative structure analysis of the multi-domain, cell envelope proteases of lactic acid bacteria
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10535647/
https://www.ncbi.nlm.nih.gov/pubmed/37764099
http://dx.doi.org/10.3390/microorganisms11092256
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