Title:	IGF-dependent dynamic modulation of a protease cleavage site in the intrinsically disordered linker domain of human IGFBP2
Authors:	Jaipuria, Garima Shet, Divya Malik, Shahid Swain, Monalisa Atreya, Hanudatta S. Galea, Charles A. Slomiany, Mark G. Rosenzweig, Steven A. Forbes, Briony E. Norton, Raymond S. Mondal, Somnath
Issue Date:	20-Apr-2022
Publisher:	Wiley
Citation:	Proteins, 2022, p1-12
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.
Description:	Open Access
URI:	http://hdl.handle.net/2289/7965
ISSN:	0887-3585 1097-0134
Alternative Location:	https://doi.org/10.1002/prot.26350
Copyright:	2022 Wiley
Appears in Collections:	Research Papers (SCM)

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