6FF3

Crystal structure of Drosophila neural ectodermal development factor Imp-L1 with Human IGF-I

Summary for 6FF3

• Entry DOI: 10.2210/pdb6ff3/pdb
• Related: 1GZR 4CBP
• Descriptor: Neural/ectodermal development factor IMP-L2, Insulin-like growth factor I (3 entities in total)
• Functional Keywords: igf-i, insulin binding protein, drosophila, imaginal morphogenesis, peptide binding protein
• Biological source: Drosophila melanogaster (Fruit fly); More
• Total number of polymer chains: 2
• Total formula weight: 34954.41

Authors

Brzozowski, A.M.,Kulahin, N.,Kristensen, O.,Schluckebier, G.,Meyts, P.D.,Viola, C.M. (deposition date: 2018-01-03, release date: 2018-09-26, Last modification date: 2024-11-13)

Primary citation

Roed, N.K.,Viola, C.M.,Kristensen, O.,Schluckebier, G.,Norrman, M.,Sajid, W.,Wade, J.D.,Andersen, A.S.,Kristensen, C.,Ganderton, T.R.,Turkenburg, J.P.,De Meyts, P.,Brzozowski, A.M.
Structures of insect Imp-L2 suggest an alternative strategy for regulating the bioavailability of insulin-like hormones.
Nat Commun, 9:3860-3860, 2018

PubMed 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.

PubMed: 30242155
DOI: 10.1038/s41467-018-06192-3

Experimental method

X-RAY DIFFRACTION (2.57 Å)