8cls | pdb_00008cls
Drosophila melanogaster insulin receptor ectodomain in complex with DILP5
Structural highlights
FunctionINSR_DROME Has a ligand-stimulated tyrosine-protein kinase activity. Required for cell survival. Regulates body size and organ size by altering cell number and cell size in a cell-autonomous manner. Involved in the development of the embryonic nervous system, and is necessary for axon guidance and targeting in the visual system. Also plays a role in life-span determination.[1] [2] [3] [4] [5] [6] Publication Abstract from PubMedThe 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. Structural conservation of insulin/IGF signalling axis at the insulin receptors level in Drosophila and humans.,Viola CM, Frittmann O, Jenkins HT, Shafi T, De Meyts P, Brzozowski AM Nat Commun. 2023 Oct 7;14(1):6271. doi: 10.1038/s41467-023-41862-x. PMID:37805602[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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