西亚试剂：NotumdeacylWntproteintosuppresssignalactivity

NotumdeacylWntproteintosuppresssignalactivity

SignalbyWntproteinisfinebalanctoensurnormaldevelopandtissuhomeostasiwhileavoiddiseassuchascancer.ThiisachievinpartbyNotum

,NotumdeacylWntproteintosuppresssignalactivitynservsecretfeedbackantagonist.Notumhabeenthoughttoactasaphospholipase,

shedglypicanandassociWntproteinfromthecellsurface.However,thiviewfailtoexplainspecificity,asglypicanbindmaniextracellularligands

.HereweprovidgenetevidinDrosophilathatNotumrequirglypicantosuppressWntsignalling,butdoenotcleavtheirglycophosphatidylinositolanchor

.StructuranalysrevealglycosaminoglycanbindsiteonNotum,whichprobablhelpNotumtoco-locwithWntproteins.Theialsoidentify,attheactivsiteofhumanandDrosophilaNotum,alarghydrophobpocketthataccommodpalmitoleate.

KinetandmassspectrometranalysofhumanproteinshowthatNotumisacarboxylesterasthatremovanessentipalmitolmoietifromWntproteinandthuconstitutthefirstknownextracellularproteindeacylase.

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