Identification of host insulin binding sites on Schistosoma japonicum insulin receptors

Stephenson, Rachel J., Toth, Istvan, Liang, Jiening, Mangat, Amanjot, McManus, Donald P. and You, Hong (2016) Identification of host insulin binding sites on Schistosoma japonicum insulin receptors. PLoS One, 11 7: . doi:10.1371/journal.pone.0159704


Author Stephenson, Rachel J.
Toth, Istvan
Liang, Jiening
Mangat, Amanjot
McManus, Donald P.
You, Hong
Title Identification of host insulin binding sites on Schistosoma japonicum insulin receptors
Formatted title
Identification of host insulin binding sites on Schistosoma japonicum insulin receptors
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2016-07-21
Sub-type Article (original research)
DOI 10.1371/journal.pone.0159704
Open Access Status DOI
Volume 11
Issue 7
Total pages 17
Place of publication San Francisco, United States
Publisher Public Library of Science
Collection year 2017
Language eng
Formatted abstract
Schistosoma japonicum insulin receptors (SjIRs) have been identified as encouraging vaccine candidates. Interrupting or blocking the binding between host insulin and the schistosome insulin receptors (IRs) may result in reduced glucose uptake leading to starvation and stunting of worms with a reduction in egg output. To further understand how schistosomes are able to exploit host insulin for development and growth, and whether these parasites and their mammalian hosts compete for the same insulin source, we identified insulin binding sites on the SjIRs. Based on sequence analysis and the predicted antigenic structure of the primary sequences of the SjIRs, we designed nine and eleven peptide analogues from SjIR-1 and SjIR-2, respectively. Using the Octet RED system, we identified analogues derived from SjIR-1 (10) and SjIR-2 (20, 21 and 22) with insulin-binding sequences specific for S. japonicum. Nevertheless, the human insulin receptor (HIR) may compete with the SjIRs in binding human insulin in other positions which are important for HIR binding to insulin. However, no binding occurred between insulin and parasite analogues derived from SjIR-1 (2, 7 and 8) and SjIR-2 (14, 16 and 18) at the same locations as HIR sequences which have been shown to have strong insulin binding affinities. Importantly, we found two analogues (1 and 3), derived from SjIR-1, and two analogues (13 and 15) derived from SjIR-2, were responsible for the major insulin binding affinity in S. japonicum. These peptide analogues were shown to have more than 10 times (in KD value) stronger binding capacity for human insulin compared with peptides derived from the HIR in the same sequence positions. Paradoxically, analogues 1, 3, 13 and 15 do not appear to contain major antigenic determinants which resulted in poor antibody responses to native S. japonicum protein. This argues against their future development as peptide-vaccine candidates.


Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ
Additional Notes Article number e0159704

 
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Created: Fri, 29 Jul 2016, 10:20:44 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences