Patched 1 regulates Smoothened by controlling sterol binding to its extracellular cysteine-rich domain

Kinnebrew, Maia; E. Woolley, Rachel; Bertie Ansell, T.; F.X. Byrne, Eamon; Frigui, Sara; Luchetti, Giovanni; Sircar, Ria; Nachtergaele, Sigrid; Mydock‐McGrane, Laurel; Krishnan, Kathiresan; Newstead, Simon; S.P. Sansom, Mark; F. Covey, Douglas; Siebold, Christian; Rohatgi, Rajat

doi:10.1126/sciadv.abm5563

Public

Patched 1 regulates Smoothened by controlling sterol binding to its extracellular cysteine-rich domain

Published in Science Advances • Jun 3, 2022

Authors:

Maia Kinnebrew

Rachel E. Woolley

T. Bertie Ansell

Abstract

Smoothened (SMO) transduces the Hedgehog (Hh) signal across the plasma membrane in response to accessible cholesterol. Cholesterol binds SMO at two sites: one in the extracellular cysteine-rich domain (CRD) and a second in the transmembrane domain (TMD). How these two sterol-binding sites mediate SM...

Subject

Smoothened

Allosteric regulation

Patched

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