Weaponization of a Hormone: Convergent Recruitment of Hyperglycemic Hormone into the Venom of Arthropod Predators

Undheim, EAB; Grimm, LL; Low, CF; Morgenstern, D; Herzig, V; Zobel-Thropp, P; Pineda, SS; Habib, R; Dziemborowicz, S; Fry, BG; Nicholson, GM; Binford, GJ; Mobli, M; King, GF

Weaponization of a Hormone: Convergent Recruitment of Hyperglycemic Hormone into the Venom of Arthropod Predators

Undheim, EAB Grimm, LL Low, CF Morgenstern, D Herzig, V Zobel-Thropp, P Pineda, SS Habib, R Dziemborowicz, S Fry, BG Nicholson, GM

Binford, GJ Mobli, M King, GF

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Publication Type:: Journal Article
Citation:: Structure, 2015, 23 (7), pp. 1283 - 1292
Issue Date:: 2015-07-09

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Field	Value	Language
dc.contributor.author	Undheim, EAB	en_US
dc.contributor.author	Grimm, LL	en_US
dc.contributor.author	Low, CF	en_US
dc.contributor.author	Morgenstern, D	en_US
dc.contributor.author	Herzig, V	en_US
dc.contributor.author	Zobel-Thropp, P	en_US
dc.contributor.author	Pineda, SS	en_US
dc.contributor.author	Habib, R	en_US
dc.contributor.author	Dziemborowicz, S	en_US
dc.contributor.author	Fry, BG	en_US
dc.contributor.author	Nicholson, GM https://orcid.org/0000-0002-4277-4296	en_US
dc.contributor.author	Binford, GJ	en_US
dc.contributor.author	Mobli, M	en_US
dc.contributor.author	King, GF	en_US
dc.date.available	2015-05-04	en_US
dc.date.issued	2015-07-09	en_US
dc.identifier.citation	Structure, 2015, 23 (7), pp. 1283 - 1292	en_US
dc.identifier.issn	0969-2126	en_US
dc.identifier.uri	http://hdl.handle.net/10453/117822
dc.description.abstract	© 2015 Elsevier Ltd. Summary Arthropod venoms consist primarily of peptide toxins that are injected into their prey with devastating consequences. Venom proteins are thought to be recruited from endogenous body proteins and mutated to yield neofunctionalized toxins with remarkable affinity for specific subtypes of ion channels and receptors. However, the evolutionary history of venom peptides remains poorly understood. Here we show that a neuropeptide hormone has been convergently recruited into the venom of spiders and centipedes and evolved into a highly stable toxin through divergent modification of the ancestral gene. High-resolution structures of representative hormone-derived toxins revealed they possess a unique structure and disulfide framework and that the key structural adaptation in weaponization of the ancestral hormone was loss of a C-terminal α helix, an adaptation that occurred independently in spiders and centipedes. Our results raise a new paradigm for toxin evolution and highlight the value of structural information in providing insight into protein evolution.	en_US
dc.relation.ispartof	Structure	en_US
dc.relation.isbasedon	10.1016/j.str.2015.05.003	en_US
dc.subject.classification	Biophysics	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Spiders	en_US
dc.subject.mesh	Diptera	en_US
dc.subject.mesh	Nerve Tissue Proteins	en_US
dc.subject.mesh	Spider Venoms	en_US
dc.subject.mesh	Evolution, Molecular	en_US
dc.subject.mesh	Phylogeny	en_US
dc.subject.mesh	Amino Acid Sequence	en_US
dc.subject.mesh	Protein Structure, Secondary	en_US
dc.subject.mesh	Molecular Sequence Data	en_US
dc.subject.mesh	Protein Stability	en_US
dc.subject.mesh	Arthropod Proteins	en_US
dc.title	Weaponization of a Hormone: Convergent Recruitment of Hyperglycemic Hormone into the Venom of Arthropod Predators	en_US
dc.type	Journal Article
utslib.citation.volume	7	en_US
utslib.citation.volume	23	en_US
utslib.for	1115 Pharmacology and Pharmaceutical Sciences	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
utslib.for	03 Chemical Sciences	en_US
utslib.for	06 Biological Sciences	en_US
utslib.for	08 Information and Computing 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 - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Students
utslib.copyright.status	closed_access
pubs.issue	7	en_US
pubs.publication-status	Published	en_US
pubs.volume	23	en_US

Abstract:

© 2015 Elsevier Ltd. Summary Arthropod venoms consist primarily of peptide toxins that are injected into their prey with devastating consequences. Venom proteins are thought to be recruited from endogenous body proteins and mutated to yield neofunctionalized toxins with remarkable affinity for specific subtypes of ion channels and receptors. However, the evolutionary history of venom peptides remains poorly understood. Here we show that a neuropeptide hormone has been convergently recruited into the venom of spiders and centipedes and evolved into a highly stable toxin through divergent modification of the ancestral gene. High-resolution structures of representative hormone-derived toxins revealed they possess a unique structure and disulfide framework and that the key structural adaptation in weaponization of the ancestral hormone was loss of a C-terminal α helix, an adaptation that occurred independently in spiders and centipedes. Our results raise a new paradigm for toxin evolution and highlight the value of structural information in providing insight into protein evolution.

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http://hdl.handle.net/10453/117822