8CLS

Drosophila melanogaster insulin receptor ectodomain in complex with DILP5

Summary for 8CLS

• Entry DOI: 10.2210/pdb8cls/pdb
• EMDB information: 16718
• Descriptor: Insulin-like receptor, Probable insulin-like peptide 5 A chain, Probable insulin-like peptide 5 (3 entities in total)
• Functional Keywords: dilp5 hormone, drosophila insulin-like signalling receptor, disulfide linked ectodomain, signaling protein
• Biological source: Drosophila melanogaster (fruit fly); More
• Total number of polymer chains: 8
• Total formula weight: 257590.38

Authors

Viola, C.M.,Brzozowski, A.M.,Shafi, T. (deposition date: 2023-02-17, release date: 2023-12-20, Last modification date: 2024-10-16)

Primary citation

Viola, C.M.,Frittmann, O.,Jenkins, H.T.,Shafi, T.,De Meyts, P.,Brzozowski, A.M.
Structural conservation of insulin/IGF signalling axis at the insulin receptors level in Drosophila and humans.
Nat Commun, 14:6271-6271, 2023

PubMed Abstract: The insulin-related hormones regulate key life processes in Metazoa, from metabolism to growth, lifespan and aging, through an evolutionarily conserved insulin signalling axis (IIS). In humans the IIS axis is controlled by insulin, two insulin-like growth factors, two isoforms of the insulin receptor (hIR-A and -B), and its homologous IGF-1R. In Drosophila, this signalling engages seven insulin-like hormones (DILP1-7) and a single receptor (dmIR). This report describes the cryoEM structure of the dmIR ectodomain:DILP5 complex, revealing high structural homology between dmIR and hIR. The excess of DILP5 yields dmIR complex in an asymmetric 'T' conformation, similar to that observed in some complexes of human IRs. However, dmIR binds three DILP5 molecules in a distinct arrangement, showing also dmIR-specific features. This work adds structural support to evolutionary conservation of the IIS axis at the IR level, and also underpins a better understanding of an important model organism.

PubMed: 37805602
DOI: 10.1038/s41467-023-41862-x

Experimental method

ELECTRON MICROSCOPY (4 Å)