Structures and pH-dependent dimerization of the Sevenless receptor tyrosine kinase. Cerutti et al.

Published: 14 October 2024| Version 1 | DOI: 10.17632/vwpfw4357x.1
Contributors:
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, Lawrence Shapiro

Description

Sevenless (Sev) is a Drosophila receptor tyrosine kinase (RTK) required for the specification of the R7 photoreceptor. It is cleaved into alpha and beta 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 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.

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Institutions

Columbia University

Categories

Biochemistry, Genetics, Developmental Biology, Structural Biology, Biophysics, Protein-Protein Interaction

Funding

National Institutes of Health

EY026217

National Institutes of Health

EY023635

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