It is time for top-down venomics

 

Rafael D. Melani¹, Fabio C. S. Nogueira¹, Gilberto B. Domont¹

 

1 Proteomics Unit, Department of Biochemistry, Institute of Chemistry, Federal University of Rio de Janeiro, Av. Athos da Silveira Ramos, 149, CT A-542, Cidade Universitária, Rio de Janeiro, RJ CEP 21941-909, Brazil

 

ABSTRACT

The protein composition of animal venoms is usually determined by peptide-centric proteomics approaches (bottom-up proteomics). However, this technique cannot, in most cases, distinguish among toxin proteoforms, herein called toxiforms, because of the protein inference problem. Top-down proteomics (TDP) analyzes intact proteins without digestion and provides high quality data to identify and characterize toxiforms. Denaturing top-down proteomics is the most disseminated subarea of TDP, which performs qualitative and quantitative analyzes of proteoforms up to ~30 kDa in high-throughput and automated fashion. On the other hand, native top-down proteomics provides access to information on large proteins (> 50 kDA) and protein interactions preserving non-covalent bonds and physiological complex stoichiometry. The use of native and denaturing top-down venomics introduced novel and useful techniques to toxinology, allowing an unprecedented characterization of venom proteins and protein complexes at the toxiform level. The collected data contribute to a deep understanding of venom natural history, open new possibilities to study the toxin evolution, and help in the development of better biotherapeutics.

 

Key words: Venomics; Toxiforms; Top-down proteomics; Denaturing top-down proteomics; Native top-down proteomics

 

Funding

RDM is National Council for Scientific and Technological Development (CNPq), Brazil, post-doctoral fellow under award number 150232/2016–0. FCSN is FAPERJ fellow, grant E-26/202.801/2015. GBD is fellow of the National Council for Scientific and Technological Development, CNPq, Brazil (Grant 306,316/2015–3).

 

Received: May 19, 2017.

Revised: September 21, 2017.

Accepted: October 18, 2017.

 

Correspondence: melanirafael@yahoo.com.br; gilberto@iq.ufrj.br

 

Authors’ contributions

RDM drafted the manuscript and all authors contributed writing and revising the manuscript. All authors read and approved the final version of the manuscript.

 

Ethics approval and consent to participate

Not applicable.

 

Consent for publication

Not applicable.

 

Competing interests

The authors declare that they have no competing interests.

 

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