Molecular basis of Cyclin B1-CDK1 recruitment by MAD1

A MAD1 short linear motif binds Cyclin B1 with a non-canonical helical mode, using hydrophobic contacts that overlap RxL recognition yet preferentially select B-type cyclins.

• Why it matters: Cyclin B1-CDK1 recruitment by MAD1 sustains spindle assembly checkpoint signaling at the nuclear pore complex and kinetochore corona, but the molecular recognition rules were unclear.
• What they did: The authors combined deep mutational scanning, cryogenic electron microscopy, and binding affinity measurements to map how the MAD1 motif engages Cyclin B1 and test its functional sufficiency in mitotic cells.
• The result: The MAD1 motif binds as an -helix to the RxL-binding hydrophobic patch, enabling B-type cyclin-specific substrate phosphorylation in mitotic cells and suggesting therapeutic targeting strategies.

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