MHJ-0125 is an M42 glutamyl aminopeptidase that moonlights as a multifunctional adhesin on the surface of Mycoplasma hyopneumoniae

Robinson, MW; Buchtmann, KA; Jenkins, C; Tacchi, JL; Raymond, BBA; To, J; Chowdhury, PR; Woolley, LK; Labbate, M; Turnbull, L; Whitchurch, CB; Padula, MP; Djordjevic, SP

MHJ-0125 is an M42 glutamyl aminopeptidase that moonlights as a multifunctional adhesin on the surface of Mycoplasma hyopneumoniae

Robinson, MW

Buchtmann, KA Jenkins, C

Tacchi, JL Raymond, BBA

To, J

Chowdhury, PR

Woolley, LK Labbate, M

Turnbull, L

Whitchurch, CB

Padula, MP

Djordjevic, SP

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Publication Type:: Journal Article
Citation:: Open Biology, 2013, 3 (APR)
Issue Date:: 2013-01-01

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Field	Value	Language
dc.contributor.author	Robinson, MW https://orcid.org/0000-0001-7191-0034	en_US
dc.contributor.author	Buchtmann, KA	en_US
dc.contributor.author	Jenkins, C https://orcid.org/0000-0002-5966-072X	en_US
dc.contributor.author	Tacchi, JL	en_US
dc.contributor.author	Raymond, BBA https://orcid.org/0000-0003-3610-9289	en_US
dc.contributor.author	To, J https://orcid.org/0000-0003-3482-4369	en_US
dc.contributor.author	Chowdhury, PR https://orcid.org/0000-0003-4352-603X	en_US
dc.contributor.author	Woolley, LK	en_US
dc.contributor.author	Labbate, M https://orcid.org/0000-0003-1428-3382	en_US
dc.contributor.author	Turnbull, L https://orcid.org/0000-0002-9255-9033	en_US
dc.contributor.author	Whitchurch, CB https://orcid.org/0000-0003-2296-3791	en_US
dc.contributor.author	Padula, MP https://orcid.org/0000-0002-8283-0643	en_US
dc.contributor.author	Djordjevic, SP https://orcid.org/0000-0001-9301-5372	en_US
dc.date.issued	2013-01-01	en_US
dc.identifier.citation	Open Biology, 2013, 3 (APR)	en_US
dc.identifier.uri	http://hdl.handle.net/10453/32701
dc.description.abstract	Bacterial aminopeptidases play important roles in pathogenesis by providing a source of amino acids from exogenous proteins, destroying host immunological effector peptides and executing posttranslational modification of bacterial and host proteins. We show that MHJ-0125 from the swine respiratory pathogen Mycoplasma hyopneumoniae represents a new member of the M42 class of bacterial aminopeptidases. Despite lacking a recognizable signal sequence, MHJ-0125 is detectable on the cell surface by fluorescence microscopy and LC-MS/MS of (i) biotinylated surface proteins captured by avidin chromatography and (ii) peptides released by mild trypsin shaving. Furthermore, surface-associated glutamyl aminopeptidase activity was detected by incubation of live M. hyopneumoniae cells with the diagnostic substrate H-Glu-AMC. MHJ-0125 moonlights as a multifunctional adhesin, binding to both heparin and plasminogen. Native proteomics and comparative modelling studies suggest MHJ-0125 forms a dodecameric, homopolymeric structure and provide insight into the positions of key residues that are predicted to interact with heparin and plasminogen. MHJ-0125 is the first aminopeptidase shown to both bind plasminogen and facilitate its activation by tissue plasminogen activator. Plasmin cleaves host extracellular matrix proteins and activates matrix metalloproteases, generating peptide substrates for MHJ-0125 and a source of amino acids for growth of M. hyopneumoniae. This unique interaction represents a new paradigm in microbial pathogenesis. © 2013 The Authors.	en_US
dc.relation.ispartof	Open Biology	en_US
dc.relation.isbasedon	10.1098/rsob.130017	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Swine	en_US
dc.subject.mesh	Mycoplasma hyopneumoniae	en_US
dc.subject.mesh	Plasminogen	en_US
dc.subject.mesh	Glutamyl Aminopeptidase	en_US
dc.subject.mesh	Heparin	en_US
dc.subject.mesh	Bacterial Proteins	en_US
dc.subject.mesh	Adhesins, Bacterial	en_US
dc.subject.mesh	Recombinant Proteins	en_US
dc.subject.mesh	Sequence Alignment	en_US
dc.subject.mesh	Proteomics	en_US
dc.subject.mesh	Phylogeny	en_US
dc.subject.mesh	Amino Acid Sequence	en_US
dc.subject.mesh	Protein Structure, Tertiary	en_US
dc.subject.mesh	Protein Binding	en_US
dc.subject.mesh	Models, Molecular	en_US
dc.subject.mesh	Molecular Sequence Data	en_US
dc.title	MHJ-0125 is an M42 glutamyl aminopeptidase that moonlights as a multifunctional adhesin on the surface of Mycoplasma hyopneumoniae	en_US
dc.type	Journal Article
utslib.citation.volume	APR	en_US
utslib.citation.volume	3	en_US
utslib.for	0605 Microbiology	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
utslib.for	1107 Immunology	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/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - ithree - Institute of Infection, Immunity and Innovation
utslib.copyright.status	open_access
pubs.issue	APR	en_US
pubs.publication-status	Published	en_US
pubs.volume	3	en_US

Abstract:

Bacterial aminopeptidases play important roles in pathogenesis by providing a source of amino acids from exogenous proteins, destroying host immunological effector peptides and executing posttranslational modification of bacterial and host proteins. We show that MHJ-0125 from the swine respiratory pathogen Mycoplasma hyopneumoniae represents a new member of the M42 class of bacterial aminopeptidases. Despite lacking a recognizable signal sequence, MHJ-0125 is detectable on the cell surface by fluorescence microscopy and LC-MS/MS of (i) biotinylated surface proteins captured by avidin chromatography and (ii) peptides released by mild trypsin shaving. Furthermore, surface-associated glutamyl aminopeptidase activity was detected by incubation of live M. hyopneumoniae cells with the diagnostic substrate H-Glu-AMC. MHJ-0125 moonlights as a multifunctional adhesin, binding to both heparin and plasminogen. Native proteomics and comparative modelling studies suggest MHJ-0125 forms a dodecameric, homopolymeric structure and provide insight into the positions of key residues that are predicted to interact with heparin and plasminogen. MHJ-0125 is the first aminopeptidase shown to both bind plasminogen and facilitate its activation by tissue plasminogen activator. Plasmin cleaves host extracellular matrix proteins and activates matrix metalloproteases, generating peptide substrates for MHJ-0125 and a source of amino acids for growth of M. hyopneumoniae. This unique interaction represents a new paradigm in microbial pathogenesis. © 2013 The Authors.

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http://hdl.handle.net/10453/32701