1S2H
The Mad2 spindle checkpoint protein possesses two distinct natively folded states
Summary for 1S2H
| Entry DOI | 10.2210/pdb1s2h/pdb |
| Related | 1DUJ 1KLQ |
| Descriptor | Mitotic spindle assembly checkpoint protein MAD2A (1 entity in total) |
| Functional Keywords | mad2, spindle checkpoint protein, cell cycle |
| Biological source | Homo sapiens (human) |
| Cellular location | Nucleus: Q13257 |
| Total number of polymer chains | 1 |
| Total formula weight | 23504.82 |
| Authors | Luo, X.,Tang, Z.,Xia, G.,Wassmann, K.,Matsumoto, T.,Rizo, J.,Yu, H. (deposition date: 2004-01-08, release date: 2004-03-30, Last modification date: 2024-05-22) |
| Primary citation | Luo, X.,Tang, Z.,Xia, G.,Wassmann, K.,Matsumoto, T.,Rizo, J.,Yu, H. The Mad2 spindle checkpoint protein has two distinct natively folded states. Nat.Struct.Mol.Biol., 11:338-345, 2004 Cited by PubMed Abstract: The spindle checkpoint delays chromosome segregation in response to misaligned sister chromatids during mitosis, thus ensuring the fidelity of chromosome inheritance. Through binding to Cdc20, the Mad2 spindle checkpoint protein inhibits the target of this checkpoint, the ubiquitin protein ligase APC/C(Cdc20). We now show that without cofactor binding or covalent modification Mad2 adopts two distinct folded conformations at equilibrium (termed N1-Mad2 and N2-Mad2). The structure of N2-Mad2 has been determined by NMR spectroscopy. N2-Mad2 is much more potent in APC/C inhibition. Overexpression of a Mad2 mutant that specifically sequesters N2-Mad2 partially blocks checkpoint signaling in living cells. The two Mad2 conformers interconvert slowly in vitro, but interconversion is accelerated by a fragment of Mad1, an upstream regulator of Mad2. Our results suggest that the unusual two-state behavior of Mad2 is critical for spindle checkpoint signaling. PubMed: 15024386DOI: 10.1038/nsmb748 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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