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Structure paper

TitleStructures and pH-dependent dimerization of the sevenless receptor tyrosine kinase.
Journal, issue, pagesMol Cell, Vol. 84, Issue 23, Page 4677-44690.e6, Year 2024
Publish dateDec 5, 2024
AuthorsGabriele Cerutti / Ronald Arias / Fabiana Bahna / Seetha Mannepalli / Phinikoula S Katsamba / Goran Ahlsen / Brian Kloss / Renato Bruni / Andrew Tomlinson / Lawrence Shapiro /
PubMed AbstractSevenless (Sev) is a Drosophila receptor tyrosine kinase (RTK) required for the specification of the R7 photoreceptor. It is cleaved into α and β subunits and binds the ectodomain of the G-protein- ...Sevenless (Sev) is a Drosophila receptor tyrosine kinase (RTK) required for the specification of the R7 photoreceptor. It is cleaved into α and β subunits and binds the ectodomain of the G-protein-coupled receptor bride of sevenless (Boss). Previous work showed that the Boss ectodomain could bind but not activate Sev; rather, the whole seven-pass transmembrane Boss was required. Here, we show that Sev does not need to be cleaved to function and that a single-pass transmembrane form of Boss activates Sev. We use cryo-electron microscopy and biophysical methods to determine the structural basis of ligand binding and pH-dependent dimerization of Sev, and we discuss the implications in the process of Sev activation. The Sev human homolog, receptor oncogene from sarcoma 1 (ROS1), is associated with oncogenic transformations, and we discuss their structural similarities.
External linksMol Cell / PubMed:39510067 / PubMed Central
MethodsEM (single particle)
Resolution2.78 - 4.07 Å
Structure data

44502

9bfp

EMDB-44502, PDB-9bfp:
Cryo-EM structure of Sevenless extracellular domain (monomer)
Method: EM (single particle) / Resolution: 2.78 Å

44503

9bfq

EMDB-44503, PDB-9bfq:
Cryo-EM structure of Sevenless in complex with Bride of Sevenless
Method: EM (single particle) / Resolution: 3.09 Å

44504

9bfr

EMDB-44504, PDB-9bfr:
Cryo-EM structure of Bride of Sevenless extracellular domain (dimer, Sevenless-bound form)
Method: EM (single particle) / Resolution: 3.19 Å

44505

9bfs

EMDB-44505, PDB-9bfs:
Cryo-EM structure of Sevenless extracellular domain (dimer, pH 6.6)
Method: EM (single particle) / Resolution: 3.06 Å

44507

9bfu

EMDB-44507, PDB-9bfu:
Cryo-EM structure of Sevenless extracellular domain (composite map of the dimer, pH 4.6)
Method: EM (single particle) / Resolution: 4.07 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • drosophila melanogaster (fruit fly)
KeywordsSIGNALING PROTEIN / sevenless / receptor tyrosine kinase / RTK / drosophila / eye development / vision / photoreceptor / ROS1 / bride of sevenless / boss / GPCR / G-protein coupled receptor / glucose metabolism

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