title: Weaponization of a Hormone: Convergent Recruitment of Hyperglycemic Hormone into the Venom of Arthropod Predators.
abstract: 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.
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia; Centre for Advanced Imaging, The University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Eivind A B
authors.initials: EA
authors.lastname: Undheim
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Lena L
authors.initials: LL
authors.lastname: Grimm
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Chek-Fong
authors.initials: CF
authors.lastname: Low
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Morgenstern
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Volker
authors.initials: V
authors.lastname: Herzig
authors.affiliation: Department of Biology, Lewis & Clark College, Portland, OR 97219, USA.
authors.forename: Pamela
authors.initials: P
authors.lastname: Zobel-Thropp
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Sandy Steffany
authors.initials: SS
authors.lastname: Pineda
authors.affiliation: School of Medical & Molecular Biosciences, University of Technology Sydney, Broadway, NSW 2007, Australia.
authors.forename: Rosaline
authors.initials: R
authors.lastname: Habib
authors.affiliation: School of Medical & Molecular Biosciences, University of Technology Sydney, Broadway, NSW 2007, Australia.
authors.forename: Slawomir
authors.initials: S
authors.lastname: Dziemborowicz
authors.affiliation: School of Biological Sciences, The University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Bryan G
authors.initials: BG
authors.lastname: Fry
authors.affiliation: School of Medical & Molecular Biosciences, University of Technology Sydney, Broadway, NSW 2007, Australia.
authors.forename: Graham M
authors.initials: GM
authors.lastname: Nicholson
authors.affiliation: Department of Biology, Lewis & Clark College, Portland, OR 97219, USA.
authors.forename: Greta J
authors.initials: GJ
authors.lastname: Binford
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia; Centre for Advanced Imaging, The University of Queensland, St Lucia, QLD 4072, Australia. Electronic address: m.mobli@uq.edu.au.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Mobli
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia. Electronic address: glenn.king@imb.uq.edu.au.
authors.forename: Glenn F
authors.initials: GF
authors.lastname: King
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D060829:Arthropod Proteins / Q000737:chemistry / Q000235:genetics* / Q000494:pharmacology; D004175:Diptera / Q000187:drug effects; D019143:Evolution, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010802:Phylogeny; D055550:Protein Stability; D017433:Protein Structure, Secondary; D013111:Spider Venoms / Q000737:chemistry / Q000235:genetics* / Q000494:pharmacology; D013112:Spiders / Q000235:genetics
chemical_list: D060829:Arthropod Proteins; D009419:Nerve Tissue Proteins; D013111:Spider Venoms; C041298:hyperglycemic hormone, arachnidan