Design principles of a membrane-spanning ubiquitin ligase
dlvr.it
Williams et al. report structures of the MMM complex, a membrane-spanning E3 ligase. A single α helix suspends an activated RING domain below the plasma membrane to ubiquitylate the GPCR Smoothened and attenuate Hedgehog signaling. This work establishes a structural and mechanistic blueprint for how transmembrane E3s search and destroy key receptors in development, immunity, and metabolism.
