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http://hdl.handle.net/2289/7965
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DC Field | Value | Language |
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dc.contributor.author | Jaipuria, Garima | - |
dc.contributor.author | Shet, Divya | - |
dc.contributor.author | Malik, Shahid | - |
dc.contributor.author | Swain, Monalisa | - |
dc.contributor.author | Atreya, Hanudatta S. | - |
dc.contributor.author | Galea, Charles A. | - |
dc.contributor.author | Slomiany, Mark G. | - |
dc.contributor.author | Rosenzweig, Steven A. | - |
dc.contributor.author | Forbes, Briony E. | - |
dc.contributor.author | Norton, Raymond S. | - |
dc.contributor.author | Mondal, Somnath | - |
dc.date.accessioned | 2022-06-22T05:29:39Z | - |
dc.date.available | 2022-06-22T05:29:39Z | - |
dc.date.issued | 2022-04-20 | - |
dc.identifier.citation | Proteins, 2022, p1-12 | en_US |
dc.identifier.issn | 0887-3585 | - |
dc.identifier.issn | 1097-0134 | - |
dc.identifier.uri | http://hdl.handle.net/2289/7965 | - |
dc.description | Open Access | en_US |
dc.description.abstract | Functional 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.iso | en | en_US |
dc.publisher | Wiley | en_US |
dc.relation.uri | https://doi.org/10.1002/prot.26350 | en_US |
dc.rights | 2022 Wiley | en_US |
dc.title | IGF-dependent dynamic modulation of a protease cleavage site in the intrinsically disordered linker domain of human IGFBP2 | en_US |
dc.type | Article | en_US |
Appears in Collections: | Research Papers (SCM) |
Files in This Item:
File | Description | Size | Format | |
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2022_Proteins_1-12.pdf | Open Access | 4.66 MB | Adobe PDF | View/Open |
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