Structural mechanisms of SAMD9 autoinhibition and pathogenic dysregulation.

Abstract excerpt

SAMD9 and SAMD9L (SAMD9/9L) are large cytosolic proteins essential for hematopoietic homeostasis and antiviral defense (1-3). Germline gain-of-function (GoF) mutations in SAMD9/9L cause severe multisystem disorders and predispose to leukemia, but the mechanisms that regulate SAMD9/9L activity and how pathogenic mutations disrupt these processes remain poorly understood. Here, we report cryo-electron microscopy...

Topics

• Humans
• Mutation
• Cryoelectron Microscopy
• Models, Molecular
• Protein Conformation
• Protein Multimerization