Protein Metamorphosis: The Two-State Behavior of Mad2
By Xuelian Luo, Hongtao Yu. 2008
156 citations recorded by the source corpus.
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.
Subfields: Cell Biology, Molecular Biology
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Citations in the corpus
- Predicting multiple conformations via sequence clustering and AlphaFold2 (2023, neutral): “In the closed state, the C-terminal β-hairpin rear-range into a new β-hairpin that binds to a completely different site, displacing the original N-terminal β-strand 28 (Fig.”
- Mutational tipping points for switching protein folds and functions (2012, unknown): “, 2008), Mad2 (Luo and Yu, 2008; Mapelli and Musacchio, 2007), and CLIC1 (Littler et al.”
- Prediction of multiple conformational states by combining sequence clustering with AlphaFold2 (2022, background): “In the closed state, the C-terminal beta-hairpin rearrange into a new β -hairpin that binds to a completely different site, displacing the original N-terminal β -strand 16 ( Figure 4C ).”