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dc.contributor.authorRenteria, Miguel
dc.contributor.authorGandhi, Neha
dc.contributor.authorVinuesa, P.
dc.contributor.authorHelmerhorst, Erik
dc.contributor.authorMancera, Ricardo
dc.date.accessioned2017-01-30T13:09:12Z
dc.date.available2017-01-30T13:09:12Z
dc.date.created2009-03-05T00:55:47Z
dc.date.issued2008
dc.date.submitted2009-11-11
dc.identifier.citationRenteria, Miguel and Gandhi, Neha and Vinuesa, Pablo and Helmerhorst, Erik and Mancera, Ricardo. 2008. A comparative structural bioinformatics analysis of the insulin receptor family ectodomain based on phylogenetic information. PLoS ONE. 3 (11): pp. 1-15.
dc.identifier.urihttp://hdl.handle.net/20.500.11937/29028
dc.identifier.doi10.1371/journal.pone.0003667
dc.description.abstract

The insulin receptor (IR), the insulin-like growth factor 1 receptor (IGF1R) and the insulin receptor-related receptor (IRR) are covalently-linked homodimers made up of several structural domains. The molecular mechanism of ligand binding to the ectodomain of these receptors and the resulting activation of their tyrosine kinase domain is still not well understood. We have carried out an amino acid residue conservation analysis in order to reconstruct the phylogeny of the IR Family. We have confirmed the location of ligand binding site 1 of the IGF1R and IR. Importantly, we have also predicted the likely location of the insulin binding site 2 on the surface of the fibronectin type III domains of the IR. An evolutionary conserved surface on the second leucine-rich domain that may interact with the ligand could not be detected. We suggest a possible mechanical trigger of the activation of the IR that involves a slight 'twist' rotation of the last two fibronectin type III domains in order to face the likely location of insulin. Finally, a strong selective pressure was found amongst the IRR orthologous sequences, suggesting that this orphan receptor has a yet unknown physiological role which may be conserved from amphibians to mammals.

dc.publisherPublic Library of Science (PLoS)
dc.titleA comparative structural bioinformatics analysis of the insulin receptor family ectodomain based on phylogenetic information
dc.typeJournal Article
dcterms.dateSubmitted2009-03-05
dcterms.source.volume3
dcterms.source.number11
dcterms.source.startPage1
dcterms.source.endPage15
dcterms.source.issn19326203
dcterms.source.titlePLoS ONE
curtin.digitool.pid117028
curtin.note

The link to the journal’s home page is: http://www.plosone.org/home.action

curtin.note

Copyright: © 2008 Rentería et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

curtin.pubStatusPublished
curtin.identifier.scriptidPUB-HEA-SBS-AJS-46341
curtin.accessStatusOpen access
curtin.facultyFaculty of Health Sciences
curtin.facultySchool of Biomedical Sciences


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