Please use this identifier to cite or link to this item: http://hdl.handle.net/2289/7965
Full metadata record
DC FieldValueLanguage
dc.contributor.authorJaipuria, Garima-
dc.contributor.authorShet, Divya-
dc.contributor.authorMalik, Shahid-
dc.contributor.authorSwain, Monalisa-
dc.contributor.authorAtreya, Hanudatta S.-
dc.contributor.authorGalea, Charles A.-
dc.contributor.authorSlomiany, Mark G.-
dc.contributor.authorRosenzweig, Steven A.-
dc.contributor.authorForbes, Briony E.-
dc.contributor.authorNorton, Raymond S.-
dc.contributor.authorMondal, Somnath-
dc.date.accessioned2022-06-22T05:29:39Z-
dc.date.available2022-06-22T05:29:39Z-
dc.date.issued2022-04-20-
dc.identifier.citationProteins, 2022, p1-12en_US
dc.identifier.issn0887-3585-
dc.identifier.issn1097-0134-
dc.identifier.urihttp://hdl.handle.net/2289/7965-
dc.descriptionOpen Accessen_US
dc.description.abstractFunctional regulation via conformational dynamics is well known in structured proteins but less well characterized in intrinsically disordered proteins and their complexes. Using NMR spectroscopy, we have identified a dynamic regulatory mechanism in the human insulin-like growth factor (IGF) system involving the central, intrinsically disordered linker domain of human IGF-binding protein-2 (hIGFBP2). The bioavailability of IGFs is regulated by the proteolysis of IGF-binding proteins. In the case of hIGFBP2, the linker domain (L-hIGFBP2) retains its intrinsic disorder upon binding IGF-1, but its dynamics are significantly altered, both in the IGF binding region and distantly located protease cleavage sites. The increase in flexibility of the linker domain upon IGF-1 binding may explain the IGF-dependent modulation of proteolysis of IGFBP2 in this domain. As IGF homeostasis is important for cell growth and function, and its dysregulation is a key contributor to several cancers, our findings open up new avenues for the design of IGFBP analogs inhibiting IGF-dependent tumors.en_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.urihttps://doi.org/10.1002/prot.26350en_US
dc.rights2022 Wileyen_US
dc.titleIGF-dependent dynamic modulation of a protease cleavage site in the intrinsically disordered linker domain of human IGFBP2en_US
dc.typeArticleen_US
Appears in Collections:Research Papers (SCM)

Files in This Item:
File Description SizeFormat 
2022_Proteins_1-12.pdfOpen Access4.66 MBAdobe PDFView/Open


Items in RRI Digital Repository are protected by copyright, with all rights reserved, unless otherwise indicated.