Editors' ChoiceStructural Biology

An interaction that guides cell fate

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Sci. Signal.  24 Feb 2015:
Vol. 8, Issue 365, pp. ec46
DOI: 10.1126/scisignal.aaa9569

Notch signaling is important in cell fate determination in mammals. Signaling is initiated when the extracellular domain of the transmembrane Notch protein on one cell binds to a surface-exposed ligand on another cell. Luca et al. report the crystal structure of the interacting regions of Notch and the Delta-like ligand DLL-4. The Notch protein is modified by O-linked glycan addition, and this is required for signaling. The structure shows two interaction interfaces. A glycan anchors the less conserved interface, which potentially provides a flexible way of regulating Notch interactions during development.

V. C. Luca, K. M. Jude, N. W. Pierce, M. V. Nachury, S. Fischer, K. C. Garcia, Structural basis for Notch1 engagement of Delta-like 4. Science 347, 847–853 (2015). [Abstract] [Full Text]