Structures of insect Imp-L2 suggest an alternative strategy for regulating the bioavailability of insulin-like hormones
Nikolaj Kulahin Roed, Cristina M Viola, Ole Kristensen, Gerd Schluckebier, Mathias Norrman, Waseem Sajid, John D Wade, Asser Sloth Andersen, Claus Kristensen, Timothy R Ganderton, Johan P Turkenburg, Pierre De Meyts, Andrzej M Brzozowski
Nature Communications | NATURE PUBLISHING GROUP | Published : 2018
The insulin/insulin-like growth factor signalling axis is an evolutionary ancient and highly conserved hormonal system involved in the regulation of metabolism, growth and lifespan in animals. Human insulin is stored in the pancreas, while insulin-like growth factor-1 (IGF-1) is maintained in blood in complexes with IGF-binding proteins (IGFBP1-6). Insect insulin-like polypeptide binding proteins (IBPs) have been considered as IGFBP-like structural and functional homologues. Here, we report structures of the Drosophila IBP Imp-L2 in its free form and bound to Drosophila insulin-like peptide 5 and human IGF-1. Imp-L2 contains two immunoglobulin-like fold domains and its architecture is unrela..View full abstract
Awarded by Medical Research Council
Awarded by NHMRC Principal Research Fellowship
A.M.B., T.R.G., C.M.V. work was supported by the Medical Research Council (Grant MR/K000179/1 and MR/R009066/1 to A.M.B.). J.D.W. is supported by an NHMRC Principal Research Fellowship (1117483). We thank Maxlab (Lund, Sweden), ESRF Grenoble and Diamond Light Source (proposal numbers mx-1221 and mx-7864) for access to their beam lines that contributed to the results presented here. We thank Mr. Sam Hart for assistance with data collection, and Chris Watson for crystallizations.