Structural Basis of Neurohormone Perception by the Receptor Tyrosine Kinase Torso

Simon Jenni, Yogesh Goyal, Marcin von Grotthuss, Stanislav Y. Shvartsman, Daryl E. Klein

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

In 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.

Original languageEnglish (US)
Pages (from-to)941-952
Number of pages12
JournalMolecular Cell
Volume60
Issue number6
DOIs
StatePublished - Dec 17 2015

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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