title: The Mad2 partial unfolding model: regulating mitosis through Mad2 conformational switching.
abstract: The metamorphic Mad2 protein acts as a molecular switch in the checkpoint mechanism that monitors proper chromosome attachment to spindle microtubules during cell division. The remarkably slow spontaneous rate of Mad2 switching between its checkpoint inactive and active forms is catalyzed onto a physiologically relevant time scale by a self-self interaction between its two forms, culminating in a large pool of active Mad2. Recent structural, biochemical, and cell biological advances suggest that the catalyzed conversion of Mad2 requires a major structural rearrangement that transits through a partially unfolded intermediate.
authors.affiliation: Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Skinner
authors.forename: Stacey
authors.initials: S
authors.lastname: Wood
authors.forename: James
authors.initials: J
authors.lastname: Shorter
authors.forename: S Walter
authors.initials: SW
authors.lastname: Englander
authors.forename: Ben E
authors.initials: BE
authors.lastname: Black
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D002384:Catalysis; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D064246:Mad2 Proteins; D008938:Mitosis / Q000502:physiology*; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000378:metabolism; D011328:Prions / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D055503:Protein Multimerization; D012097:Repressor Proteins / Q000737:chemistry* / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; C501384:MAD1L1 protein, human; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D009687:Nuclear Proteins; D011328:Prions; D012097:Repressor Proteins