The Mad2 spindle checkpoint protein undergoes similar major conformational changes upon binding to either Mad1 or Cdc20

Mol Cell. 2002 Jan;9(1):59-71. doi: 10.1016/s1097-2765(01)00435-x.

Abstract

Mad2 participates in spindle checkpoint inhibition of APC(Cdc20). We show that RNAi-mediated suppression of Mad1 function in mammalian cells causes loss of Mad2 kinetochore localization and impairment of the spindle checkpoint. Mad1 and Cdc20 contain Mad2 binding motifs that share a common consensus. We have identified a class of Mad2 binding peptides with a similar consensus. Binding of one of these ligands, MBP1, triggers an extensive rearrangement of the tertiary structure of Mad2. Mad2 also undergoes a similar striking structural change upon binding to a Mad1 or Cdc20 binding motif peptide. Our data suggest that, upon checkpoint activation, Mad1 recruits Mad2 to unattached kinetochores and may promote binding of Mad2 to Cdc20.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Calcium-Binding Proteins / chemistry
  • Calcium-Binding Proteins / metabolism*
  • Cdc20 Proteins
  • Cell Cycle Proteins*
  • HeLa Cells
  • Humans
  • Ligands
  • Mad2 Proteins
  • Models, Molecular
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism
  • Phosphoproteins / chemistry
  • Phosphoproteins / metabolism*
  • Protein Binding
  • Protein Conformation
  • Proteins / chemistry
  • Proteins / metabolism*
  • Repressor Proteins / chemistry
  • Repressor Proteins / metabolism*

Substances

  • Calcium-Binding Proteins
  • Cdc20 Proteins
  • Cell Cycle Proteins
  • Ligands
  • MAD1L1 protein, human
  • MAD2L1 protein, human
  • Mad2 Proteins
  • Nuclear Proteins
  • Phosphoproteins
  • Proteins
  • Repressor Proteins
  • CDC20 protein, human