9BFP

Cryo-EM structure of Sevenless extracellular domain (monomer)

Summary for 9BFP

• Entry DOI: 10.2210/pdb9bfp/pdb
• Related: 9BFQ 9BFR 9BFS 9BFU
• EMDB information: 44502
• Descriptor: Protein sevenless, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: sevenless, receptor tyrosine kinase, rtk, drosophila, eye development, vision, photoreceptor, ros1, signaling protein
• Biological source: Drosophila melanogaster (fruit fly)
• Total number of polymer chains: 1
• Total formula weight: 226159.74

Authors

Cerutti, G.,Shapiro, L. (deposition date: 2024-04-18, release date: 2025-01-29, Last modification date: 2025-05-14)

Primary citation

Cerutti, G.,Arias, R.,Bahna, F.,Mannepalli, S.,Katsamba, P.S.,Ahlsen, G.,Kloss, B.,Bruni, R.,Tomlinson, A.,Shapiro, L.
Structures and pH-dependent dimerization of the sevenless receptor tyrosine kinase.
Mol.Cell, 84:4677-4690.e6, 2024

PubMed Abstract: 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.

PubMed: 39510067
DOI: 10.1016/j.molcel.2024.10.017

Experimental method

ELECTRON MICROSCOPY (2.78 Å)