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Mechanism of midline defect‐causing mutation P151L in MID1 revealed

The P151L mutation in the B-box1 domain of MID1 causes midline defects in X-linked Opitz G Syndrome. MID1 is known to be a key regulator of phosphatase PP2A through formation of a complex with its catalytic (PP2Ac) and regulatory (α4) subunits. Wright et al. show that this mutation retains B-box1 domain structure and E3 ligase activity (star) but blocks interaction with α4, indicating disruption of the MID1-α4-PP2Ac complex.