Non-proteolytic functions of microbial proteases increase pathological complexity

Jarocki, VM; Tacchi, JL; Djordjevic, SP

Non-proteolytic functions of microbial proteases increase pathological complexity

Jarocki, VM

Tacchi, JL Djordjevic, SP

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Publication Type:: Journal Article
Citation:: Proteomics, 2015, 15 (5-6), pp. 1075 - 1088
Issue Date:: 2015-01-01

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Field	Value	Language
dc.contributor.author	Jarocki, VM https://orcid.org/0000-0003-1249-0994	en_US
dc.contributor.author	Tacchi, JL	en_US
dc.contributor.author	Djordjevic, SP https://orcid.org/0000-0001-9301-5372	en_US
dc.date.available	2014-12-05	en_US
dc.date.issued	2015-01-01	en_US
dc.identifier.citation	Proteomics, 2015, 15 (5-6), pp. 1075 - 1088	en_US
dc.identifier.issn	1615-9853	en_US
dc.identifier.uri	http://hdl.handle.net/10453/43431
dc.description.abstract	© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Proteases are enzymes that catalyse hydrolysis of peptide bonds thereby controlling the shape, size, function, composition, turnover and degradation of other proteins. In microbes, proteases are often identified as important virulence factors and as such have been targets for novel drug design. It is emerging that some proteases possess additional non-proteolytic functions that play important roles in host epithelia adhesion, tissue invasion and in modulating immune responses. These additional "moonlighting" functions have the potential to obfuscate data interpretation and have implications for therapeutic design. Moonlighting enzymes comprise a subcategory of multifunctional proteins that possess at least two distinct biological functions on a single polypeptide chain. Presently, identifying moonlighting proteins relies heavily on serendipitous empirical data with clues arising from proteins lacking signal peptides that are localised to the cell surface. Here, we describe examples of microbial proteases with additional non-proteolytic functions, including streptococcal pyrogenic exotoxin B, PepO and C5a peptidases, mycoplasmal aminopeptidases, mycobacterial chaperones and viral papain-like proteases. We explore how these non-proteolytic functions contribute to host cell adhesion, modulate the coagulation pathway, assist in non-covalent folding of proteins, participate in cell signalling, and increase substrate repertoire. We conclude by describing how proteomics has aided in moonlighting protein discovery, focusing attention on potential moonlighters in microbial exoproteomes.	en_US
dc.relation.ispartof	Proteomics	en_US
dc.relation.isbasedon	10.1002/pmic.201400386	en_US
dc.subject.classification	Biochemistry & Molecular Biology	en_US
dc.subject.mesh	Bacteria	en_US
dc.subject.mesh	Peptide Hydrolases	en_US
dc.subject.mesh	Bacterial Proteins	en_US
dc.subject.mesh	Proteome	en_US
dc.subject.mesh	Virulence Factors	en_US
dc.subject.mesh	Proteomics	en_US
dc.title	Non-proteolytic functions of microbial proteases increase pathological complexity	en_US
dc.type	Journal Article
utslib.citation.volume	5-6	en_US
utslib.citation.volume	15	en_US
utslib.for	0605 Microbiology	en_US
utslib.for	1107 Immunology	en_US
utslib.for	06 Biological Sciences	en_US
utslib.for	08 Information and Computing Sciences	en_US
utslib.for	11 Medical and Health Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - ithree - Institute of Infection, Immunity and Innovation
utslib.copyright.status	closed_access
pubs.issue	5-6	en_US
pubs.publication-status	Published	en_US
pubs.volume	15	en_US

Abstract:

© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Proteases are enzymes that catalyse hydrolysis of peptide bonds thereby controlling the shape, size, function, composition, turnover and degradation of other proteins. In microbes, proteases are often identified as important virulence factors and as such have been targets for novel drug design. It is emerging that some proteases possess additional non-proteolytic functions that play important roles in host epithelia adhesion, tissue invasion and in modulating immune responses. These additional "moonlighting" functions have the potential to obfuscate data interpretation and have implications for therapeutic design. Moonlighting enzymes comprise a subcategory of multifunctional proteins that possess at least two distinct biological functions on a single polypeptide chain. Presently, identifying moonlighting proteins relies heavily on serendipitous empirical data with clues arising from proteins lacking signal peptides that are localised to the cell surface. Here, we describe examples of microbial proteases with additional non-proteolytic functions, including streptococcal pyrogenic exotoxin B, PepO and C5a peptidases, mycoplasmal aminopeptidases, mycobacterial chaperones and viral papain-like proteases. We explore how these non-proteolytic functions contribute to host cell adhesion, modulate the coagulation pathway, assist in non-covalent folding of proteins, participate in cell signalling, and increase substrate repertoire. We conclude by describing how proteomics has aided in moonlighting protein discovery, focusing attention on potential moonlighters in microbial exoproteomes.

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http://hdl.handle.net/10453/43431