Unlocking the MIT gate: STAM activates AMSH autoinhibition
Linda Makhlouf1, Elton Zeqiraj1
1Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
Abstract:
In this issue of Structure, Chen et al.1 reveal how STAMBP/AMSH, a key deubiquitinase (DUB) in endosomal sorting, is autoinhibited by its microtubule-interacting and transport (MIT) domain blocking the catalytic site. STAM and ubiquitin chains relieve this inhibition, enabling activation. These findings uncover a tuneable regulatory mechanism in DUB activity and endosomal trafficking.
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