Investigation of the interaction of β-methylamino-l-alanine with eukaryotic and prokaryotic proteins

Main, BJ; Italiano, CJ; Rodgers, KJ

Investigation of the interaction of β-methylamino-l-alanine with eukaryotic and prokaryotic proteins

Main, BJ

Italiano, CJ Rodgers, KJ

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Publication Type:: Journal Article
Citation:: Amino Acids, 2018, 50 (3-4), pp. 397 - 407
Issue Date:: 2018-04-01

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Field	Value	Language
dc.contributor.author	Main, BJ https://orcid.org/0000-0003-4719-2444	en_US
dc.contributor.author	Italiano, CJ	en_US
dc.contributor.author	Rodgers, KJ https://orcid.org/0000-0002-3627-9651	en_US
dc.date.available	2017-12-05	en_US
dc.date.issued	2018-04-01	en_US
dc.identifier.citation	Amino Acids, 2018, 50 (3-4), pp. 397 - 407	en_US
dc.identifier.issn	0939-4451	en_US
dc.identifier.uri	http://hdl.handle.net/10453/124980
dc.description.abstract	© 2017, Springer-Verlag GmbH Austria, part of Springer Nature. There is a strong body of evidence linking the non-protein amino acid (NPAA) β-methylamino-l-alanine (BMAA) to the development of a number of neurodegenerative diseases. BMAA has been found globally, is produced by a number of organisms including cyanobacteria, diatoms, and dinoflagellates; and has been shown to biomagnify through trophic levels. The role of BMAA in neurodegenerative disease is highlighted by its presence in the brains of a number of neurodegenerative disease patients, where it was found in a protein-bound form. We have previously shown that BMAA is bound to cell proteins, and results in the upregulation of the unfolded protein response, an endoplasmic reticulum stress response activated by the presence of misfolded proteins within the cell. Structurally aberrant proteins are features of a number of neurodegenerative diseases, and further investigation of how BMAA interacts with proteins is crucial to our understanding of its toxicity. Here we use radiolabelled BMAA to investigate the interaction and binding of BMAA to eukaryotic and prokaryotic proteins. We found differences in the presence and distribution of protein-bound BMAA between E. coli and neuroblastoma cells, with an increase in binding over time only seen in the eukaryotic cells. We also found that BMAA was unable to bind to pure proteins, or cell lysate in native or denaturing conditions, indicating that biological processing is required for BMAA to bind to proteins.	en_US
dc.relation.ispartof	Amino Acids	en_US
dc.relation.isbasedon	10.1007/s00726-017-2525-z	en_US
dc.subject.classification	Biochemistry & Molecular Biology	en_US
dc.subject.mesh	Brain	en_US
dc.subject.mesh	Eukaryotic Cells	en_US
dc.subject.mesh	Prokaryotic Cells	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Dinoflagellida	en_US
dc.subject.mesh	Diatoms	en_US
dc.subject.mesh	Cyanobacteria	en_US
dc.subject.mesh	Escherichia coli	en_US
dc.subject.mesh	Neurodegenerative Diseases	en_US
dc.subject.mesh	Amino Acids, Diamino	en_US
dc.subject.mesh	Proteins	en_US
dc.title	Investigation of the interaction of β-methylamino-l-alanine with eukaryotic and prokaryotic proteins	en_US
dc.type	Journal Article
utslib.citation.volume	3-4	en_US
utslib.citation.volume	50	en_US
utslib.for	1101 Medical Biochemistry and Metabolomics	en_US
utslib.for	0304 Medicinal and Biomolecular Chemistry	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/DVC (Teaching and Learning)
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 - CHT - Health Technologies
utslib.copyright.status	closed_access
pubs.issue	3-4	en_US
pubs.publication-status	Published	en_US
pubs.volume	50	en_US

Abstract:

© 2017, Springer-Verlag GmbH Austria, part of Springer Nature. There is a strong body of evidence linking the non-protein amino acid (NPAA) β-methylamino-l-alanine (BMAA) to the development of a number of neurodegenerative diseases. BMAA has been found globally, is produced by a number of organisms including cyanobacteria, diatoms, and dinoflagellates; and has been shown to biomagnify through trophic levels. The role of BMAA in neurodegenerative disease is highlighted by its presence in the brains of a number of neurodegenerative disease patients, where it was found in a protein-bound form. We have previously shown that BMAA is bound to cell proteins, and results in the upregulation of the unfolded protein response, an endoplasmic reticulum stress response activated by the presence of misfolded proteins within the cell. Structurally aberrant proteins are features of a number of neurodegenerative diseases, and further investigation of how BMAA interacts with proteins is crucial to our understanding of its toxicity. Here we use radiolabelled BMAA to investigate the interaction and binding of BMAA to eukaryotic and prokaryotic proteins. We found differences in the presence and distribution of protein-bound BMAA between E. coli and neuroblastoma cells, with an increase in binding over time only seen in the eukaryotic cells. We also found that BMAA was unable to bind to pure proteins, or cell lysate in native or denaturing conditions, indicating that biological processing is required for BMAA to bind to proteins.

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http://hdl.handle.net/10453/124980