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XB-ART-39125
Structure. November 12, 2008; 16 (11): 1616-25.

Protein metamorphosis: the two-state behavior of Mad2.

Luo X , Yu H .


Abstract
A given protein generally has only one native tertiary fold, which is the conformation with the lowest Gibbs free energy. Mad2, a protein involved in the spindle checkpoint, however, has two natively folded states with similar Gibbs free energies. Through binding to its target Cdc20, Mad2 inhibits the multisubunit ubiquitin ligase, the anaphase-promoting complex or cyclosome (APC/C), and delays the onset of anaphase until all sister chromatids achieve bipolar attachment to the mitotic spindle. Without ligand binding or covalent modifications, Mad2 adopts two topologically and functionally distinct native folds in equilibrium under physiological conditions. The transition between the two Mad2 states is regulated by multiple mechanisms and is central to the activation and inactivation of the spindle checkpoint. This review summarizes recent structural and biochemical studies on the two-state behavior of Mad2 and discusses the generality and implications of structural malleability of proteins.

PubMed ID: 19000814
PMC ID: PMC2644451
Article link: Structure.
Grant support: GM085004 NIGMS NIH HHS , GM61542 NIGMS NIH HHS , K01 CA100292-05 NCI NIH HHS , K01 CA100292-05 NCI NIH HHS , K01 CA100292-05 NCI NIH HHS , K01 CA100292-05 NCI NIH HHS , K01 CA100292-05 NCI NIH HHS , K01 CA100292-05 NCI NIH HHS , R01 GM085004-01 NIGMS NIH HHSHoward Hughes Medical Institute , K01 CA100292 NCI NIH HHS , K01 CA100292 NCI NIH HHS , K01 CA100292 NCI NIH HHS , K01 CA100292 NCI NIH HHS , K01 CA100292 NCI NIH HHS , K01 CA100292 NCI NIH HHS , R01 GM085004 NIGMS NIH HHS

Genes referenced: cdc20 mad2l1
Antibodies referenced:
Morpholinos referenced:

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