title: Peptidomics combined with cDNA library unravel the diversity of centipede venom.
abstract: Centipedes are one of the oldest venomous arthropods using toxin as their weapon to capture prey. But little attention was focused on them and only few centipede toxins were demonstrated with activity on ion channels. Therefore, more deep works are needed to understand the diversity of centipede venom. In the present study, we use peptidomics combined with cDNA library to uncover the diversity of centipede Scolopendra subspinipes mutilans L. Koch. 192 peptides were identified by LC-MS/MS and 79 precursors were deduced by cDNA library. Surprisingly, the signal peptides of centipede toxins were more complicated than any other animal toxins and even exhibited large differences in homologues. Meanwhile, a large number of variants generated by alternative cleavage sites were detected by mass spectra. Odd number of cystein (3, 5, 7) found in the mature peptides were seldom seen in peptide toxins. In additional, two novel cysteine frameworks (C-C-C-CCC, C-C-C-C-CC-CC) were identified from 16 different cysteine frameworks from centipede peptides. Only 29 precursors have clear targets, while others may provide a potential diversity function for centipede. These findings highlight the extensive diversity of centipede toxins and provide powerful tools to understand the capture and defense weapon of centipede.
  
  
  CONCLUSIONS
  Peptide toxins from venomous animal have attracted increasing attentions due to their extraordinary chemical and pharmacological diversity. Centipedes are one of the most used Chinese traditional medicines, but little was known about the active components. The venom of Scolopendra subspinipes mutilans L. Koch is first deeply analyzed in this work and most of peptides were never discovered before. Interestingly, the number and arrangement of cysteine showed a larger different to known peptide toxins such spider or scorpion toxins. Moreover, only 29 peptides from this centipede venom were identified with known function. It suggested that our work not only important to understand the composition of centipede venom, but also provide many valuable peptides for potential biological functions.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China.
authors.forename: Mingqiang
authors.initials: M
authors.lastname: Rong
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China.
authors.forename: Shilong
authors.initials: S
authors.lastname: Yang
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wen
authors.affiliation: School of Biological Sciences, Nanjing Agriculture University, Nanjing, Jiangshu 210095, China.
authors.forename: Guoxiang
authors.initials: G
authors.lastname: Mo
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China.
authors.forename: Di
authors.initials: D
authors.lastname: Kang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Zhilong
authors.initials: Z
authors.lastname: Lin
authors.affiliation: College of Life Science and Technology, Kunming University of Science and Technology, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China.
authors.forename: Bowen
authors.initials: B
authors.lastname: Li
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Chaoqin
authors.initials: C
authors.lastname: Du
authors.affiliation: Kunming Biological Diversity Regional Center of Large Apparatuses and Equipment, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China.
authors.forename: Shuanjuan
authors.initials: S
authors.lastname: Yang
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China; Kunming Biological Diversity Regional Center of Large Apparatuses and Equipment, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Feng
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Xu
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China; Kunming Biological Diversity Regional Center of Large Apparatuses and Equipment, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China; Princess Al Jawhara Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia; The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark. Electronic address: wangj@genomics.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China. Electronic address: rlai@mail.kiz.ac.cn.
authors.forename: Ren
authors.initials: R
authors.lastname: Lai
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001180:Arthropod Venoms / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001181:Arthropods / Q000235:genetics / Q000378:metabolism; D003545:Cysteine / Q000032:analysis; D015723:Gene Library; D014644:Genetic Variation; D008969:Molecular Sequence Data; D010455:Peptides / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D017386:Sequence Homology, Amino Acid; D059467:Transcriptome
chemical_list: D001180:Arthropod Venoms; D010455:Peptides; D003545:Cysteine
keywords: Centipede; Diversity; Peptidomics; Toxin