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Structures of insect Imp-L2 suggest an alternative strategy for regulating the bioavailability of insulin-like hormones

DOI: 10.1038/s41467-018-06192-3 DOI Help

Authors: Nikolaj Kulahin Roed (Novo Nordisk A/S) , Cristina M. Viola (The University of York) , Ole Kristensen (University of Copenhagen) , Gerd Schluckebier (Novo Nordisk A/S) , Mathias Norrman (Novo Nordisk A/S) , Waseem Sajid (Novo Nordisk A/S) , John D. Wade (University of Melbourne) , Asser Sloth Andersen (Novo Nordisk A/S) , Claus Kristensen (University of Copenhagen) , Timothy R. Ganderton (The University of York) , Johan P. Turkenburg (The University of York) , Pierre De Meyts (Novo Nordisk A/S) , Andrzej M. Brzozowski (The University of York)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 9

State: Published (Approved)
Published: September 2018
Diamond Proposal Number(s): 1221 , 7864

Open Access Open Access

Abstract: 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 unrelated to human IGFBPs, suggesting a distinct strategy for bioavailability regulation of insulin-like hormones. Similar hormone binding modes may exist in other insect vectors, as the IBP sequences are highly conserved. Therefore, these findings may open research routes towards a rational interference of transmission of diseases such as malaria, dengue and yellow fevers.

Journal Keywords: Insect hormones; Insulin signalling; X-ray crystallography

Subject Areas: Biology and Bio-materials, Medicine

Instruments: I03-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography

Other Facilities: Maxlab; ID14-3 at ESRF

Added On: 03/10/2018 09:59


Discipline Tags:

Infectious Diseases Health & Wellbeing Structural biology Drug Discovery Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)