TY - JOUR
T1 - Protein Metamorphosis
T2 - The Two-State Behavior of Mad2
AU - Luo, Xuelian
AU - Yu, Hongtao
N1 - Funding Information:
We thank members of our laboratories for helpful discussions and apologize to colleagues whose primary studies are not cited due to space limitations. Our research on Mad2 is supported by the National Institutes of Health (GM61542 to H.Y. and GM085004 to X.L.) and the Welch Foundation (I-1441). H.Y. is an Investigator at the Howard Hughes Medical Institute.
PY - 2008/11/12
Y1 - 2008/11/12
N2 - 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.
AB - 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.
KW - CELLBIO
KW - PROTEINS
UR - http://www.scopus.com/inward/record.url?scp=55249120526&partnerID=8YFLogxK
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U2 - 10.1016/j.str.2008.10.002
DO - 10.1016/j.str.2008.10.002
M3 - Review article
C2 - 19000814
AN - SCOPUS:55249120526
SN - 0969-2126
VL - 16
SP - 1616
EP - 1625
JO - Structure
JF - Structure
IS - 11
ER -