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

Lise Friis Christensen; Magnus Haraldson Høie; Claus Heiner Bang-Berthelsen; Paolo Marcatili; Egon Bech Hansen

doi:10.3390/microorganisms11092256

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

Lise Friis Christensen^*, Magnus Haraldson Høie, Claus Heiner Bang-Berthelsen, Paolo Marcatili, Egon Bech Hansen^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

33 Downloads (Pure)

Abstract

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.

Original language	English
Article number	2256
Journal	Microorganisms
Volume	11
Issue number	9
Number of pages	29
ISSN	2076-2607
DOIs	https://doi.org/10.3390/microorganisms11092256
Publication status	Published - 2023

Keywords

Cell envelope protease
Subtilase
Lactic acid bacteria
Protein structure
AlphaFold 2 models
Extracellular proteolysis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.3390/microorganisms11092256Licence: CC BY

FulltextFinal published version, 5.75 MBLicence: CC BY

OpenUrl availability

Full text

Cite this

@article{23b889036fac4f5f94ae930901be703a,

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

abstract = "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.",

keywords = "Cell envelope protease, Subtilase, Lactic acid bacteria, Protein structure, AlphaFold 2 models, Extracellular proteolysis",

author = "Christensen, {Lise Friis} and H{\o}ie, {Magnus Haraldson} and Bang-Berthelsen, {Claus Heiner} and Paolo Marcatili and Hansen, {Egon Bech}",

year = "2023",

doi = "10.3390/microorganisms11092256",

language = "English",

volume = "11",

journal = "Microorganisms",

issn = "2076-2607",

publisher = "M D P I AG",

number = "9",

}

TY - JOUR

T1 - Comparative Structure Analysis of the Multi-Domain, Cell Envelope Proteases of Lactic Acid Bacteria

AU - Christensen, Lise Friis

AU - Høie, Magnus Haraldson

AU - Bang-Berthelsen, Claus Heiner

AU - Marcatili, Paolo

AU - Hansen, Egon Bech

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - Cell envelope protease

KW - Subtilase

KW - Lactic acid bacteria

KW - Protein structure

KW - AlphaFold 2 models

KW - Extracellular proteolysis

U2 - 10.3390/microorganisms11092256

DO - 10.3390/microorganisms11092256

M3 - Journal article

C2 - 37764099

SN - 2076-2607

VL - 11

JO - Microorganisms

JF - Microorganisms

IS - 9

M1 - 2256

ER -

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

Abstract

Keywords

UN SDGs

Access to Document

OpenUrl availability

Fingerprint

Cite this