Structural Conservation of Insulin/IGF Signalling Axis at the Insulin Receptors Level in Drosophila and Humans
Viola, C. M.; Frittmann, O.; Jenkins, H. T.; Shafi, T.; De Meyts, P.; Brzozowski, A. M.
Show 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 hitherto-unseen arrangement, showing also dmIR-specific features. This work adds structural support to evolutionary conservation of the IIS axis at the IR level, underpinning also a better understanding of an important model organism.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Structure and dynamics of Toll immunoreceptor activation in the mosquito Aedes aegypti 95%
- Structure of the teneurin-latrophilin complex: Alternative splicing controls synapse specificity by a novel mechanism 94%
- Alternative splicing controls teneurin-3 compact dimer formation for neuronalrecognition 94%
Similar papers in this journal
- A baton-relay mechanism for ER retrieval signal capture and proofreading by the KDEL receptor 94%
- The prolactin receptor scaffolds Janus kinase 2 via co-structure formation with phosphoinositide-4,5-bisphosphate 94%
- Molecular basis for substrate specificity of the Phactr1/PP1 phosphatase holoenzyme 94%
Similar papers in this journal
- Discriminative SKP2 interactions with CDK-cyclin complexes support a cyclin A-specific role in p27KIP1 degradation 94%
- Structure and methyl-lysine binding selectivity of the HUSH complex subunit MPP8 93%
- Structural insights into the cooperative interaction of the intrinsically disordered co-activator TIF2 with retinoic acid receptor heterodimer (RXR/RAR) 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.