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

Xuelian Luo; Zhanyun Tang; Jose Rizo-Rey; Hongtao Yu

doi:10.1016/S1097-2765(01)00435-X

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

Xuelian Luo, Zhanyun Tang, Jose Rizo-Rey, Hongtao Yu

Research output: Contribution to journal › Article › peer-review

266 Scopus citations

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.

Original language	English (US)
Pages (from-to)	59-71
Number of pages	13
Journal	Molecular cell
Volume	9
Issue number	1
DOIs	https://doi.org/10.1016/S1097-2765(01)00435-X
State	Published - 2002

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1016/S1097-2765(01)00435-X

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

abstract = "Mad2 participates in spindle checkpoint inhibition of APCCdc20. 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.",

author = "Xuelian Luo and Zhanyun Tang and Jose Rizo-Rey and Hongtao Yu",

note = "Funding Information: We thank Marc Kirschner and Gerhard Wagner for encouragement and Jun Lu for assistance with structure calculation and graphics. We also thank our colleagues Hans Deisenhofer, Al Gilman, Betsy Goldsmith, and Tom S{\"u}dhof for reading the manuscript critically. X.L. is supported by a postdoctoral fellowship from the National Cancer Institute. This work is supported in part by the Welch Foundation (I1304 to J.R.) and by the Damon Runyon-Walter Winchell Foundation, the Welch Foundation (I-1441), the Burroughs Wellcome Fund, the Packard Foundation, and the National Institutes of Health (GM61542) (to H.Y.).",

year = "2002",

doi = "10.1016/S1097-2765(01)00435-X",

language = "English (US)",

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pages = "59--71",

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T1 - The Mad2 spindle checkpoint protein undergoes similar major conformational changes upon binding to either Mad1 or Cdc20

AU - Luo, Xuelian

AU - Tang, Zhanyun

AU - Rizo-Rey, Jose

AU - Yu, Hongtao

N1 - Funding Information: We thank Marc Kirschner and Gerhard Wagner for encouragement and Jun Lu for assistance with structure calculation and graphics. We also thank our colleagues Hans Deisenhofer, Al Gilman, Betsy Goldsmith, and Tom Südhof for reading the manuscript critically. X.L. is supported by a postdoctoral fellowship from the National Cancer Institute. This work is supported in part by the Welch Foundation (I1304 to J.R.) and by the Damon Runyon-Walter Winchell Foundation, the Welch Foundation (I-1441), the Burroughs Wellcome Fund, the Packard Foundation, and the National Institutes of Health (GM61542) (to H.Y.).

PY - 2002

Y1 - 2002

N2 - Mad2 participates in spindle checkpoint inhibition of APCCdc20. 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.

AB - Mad2 participates in spindle checkpoint inhibition of APCCdc20. 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.

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AN - SCOPUS:0036161468

SN - 1097-2765

VL - 9

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EP - 71

JO - Molecular cell

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

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