5aoq
Structural basis of neurohormone perception by the receptor tyrosine kinase Torso
Structural highlights
FunctionTORSO_BOMMO Probable receptor tyrosine kinase. During postembryonic development, involved in the initiation of metamorphosis probably by inducing the production of ecdysone in response to prothoracicotropic hormone (PTTH) (By similarity). Binding to PTTH stimulates activation of canonical MAPK signaling leading to ERK phosphorylation (PubMed:19965758, PubMed:26928300).[UniProtKB:P18475][1] [2] Publication Abstract from PubMedIn insects, brain-derived Prothoracicotropic hormone (PTTH) activates the receptor tyrosine kinase (RTK) Torso to initiate metamorphosis through the release of ecdysone. We have determined the crystal structure of silkworm PTTH in complex with the ligand-binding region of Torso. Here we show that ligand-induced Torso dimerization results from the sequential and negatively cooperative formation of asymmetric heterotetramers. Mathematical modeling of receptor activation based upon our biophysical studies shows that ligand pulses are "buffered" at low receptor levels, leading to a sustained signal. By contrast, high levels of Torso develop the signal intensity and duration of a noncooperative system. We propose that this may allow Torso to coordinate widely different functions from a single ligand by tuning receptor levels. Phylogenic analysis indicates that Torso is found outside arthropods, including human parasitic roundworms. Together, our findings provide mechanistic insight into how this receptor system, with roles in embryonic and adult development, is regulated. Structural Basis of Neurohormone Perception by the Receptor Tyrosine Kinase Torso.,Jenni S, Goyal Y, von Grotthuss M, Shvartsman SY, Klein DE Mol Cell. 2015 Dec 17;60(6):941-52. doi: 10.1016/j.molcel.2015.10.026. Epub 2015 , Nov 19. PMID:26698662[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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