Structural Basis of Neurohormone Perception by the Receptor Tyrosine Kinase Torso.

TitleStructural Basis of Neurohormone Perception by the Receptor Tyrosine Kinase Torso.
Publication TypeJournal Article
Year of Publication2015
AuthorsJenni, S, Goyal, Y, von Grotthuss, M, Shvartsman, SY, Klein, DE
JournalMol Cell
Volume60
Issue6
Pagination941-52
Date Published2015 Dec 17
ISSN1097-4164
KeywordsAnimals, Binding Sites, Bombyx, Crystallography, X-Ray, Gene Expression Regulation, Developmental, Humans, Insect Hormones, Insect Proteins, Models, Molecular, Phylogeny, Protein Multimerization, Receptor Protein-Tyrosine Kinases, Receptors, Interleukin-17, Signal Transduction
Abstract

<p>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.</p>

DOI10.1016/j.molcel.2015.10.026
Alternate JournalMol. Cell
PubMed ID26698662