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The Mad2 spindle checkpoint protein has two distinct natively folded states
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.
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“MAD2 has two topologically distinct monomeric structures that are in equilibrium under physiological conditions27.”
From Predicting multiple conformations via sequence clustering and AlphaFold2 (2024) · cites this paper as [27]
Citations
Cites
Crystallography & NMR System: A New Software Suite for Macromolecular Structure Determination
Brünger, A. T., Adams, P. D., Clore, G. M., DeLano, W. L., Gros, P., Grosse‐Kunstleve, R. W., Jiang, J., Kuszewski, J. J., Nilges, M., Pannu, N., et al. (1998) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444998003254 · Cited by 15,723
MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures
Kraulis, P. J. (1991) · Journal of Applied Crystallography · doi:10.1107/s0021889891004399 · Cited by 14,011
Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells
Elbashir, S. M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K., & Tuschl, T. (2001) · Nature · doi:10.1038/35078107 · Cited by 9,456
Prusiner, S. B. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.23.13363 · Cited by 5,373
[26] Raster3D: Photorealistic molecular graphics
Merritt, E. A., & Bacon, D. (1997) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(97)77028-9 · Cited by 3,749
Protein backbone angle restraints from searching a database for chemical shift and sequence homology
Cornilescu, G., Delaglio, F., & Bax, A. (1999) · Journal of Biomolecular NMR · doi:10.1023/a:1008392405740 · Cited by 2,957
Structure of influenza haemagglutinin at the pH of membrane fusion
Bullough, P. A., Hughson, F. M., Skehel, J. J., & Wiley, D. C. (1994) · Nature · doi:10.1038/371037a0 · Cited by 1,564
Program DYNAFIT for the Analysis of Enzyme Kinetic Data: Application to HIV Proteinase
Kuzmič, P. (1996) · Analytical Biochemistry · doi:10.1006/abio.1996.0238 · Cited by 1,494
Cleveland, D. W., Mao, Y., & Sullivan, K. F. (2003) · Cell · doi:10.1016/s0092-8674(03)00115-6 · Cited by 1,003
Sudakin, V., Chan, G. K. T., & Yen, T. J. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.200102093 · Cited by 927
Antibody Multispecificity Mediated by Conformational Diversity
James, L. C., Roversi, P., & Tawfik, D. S. (2003) · Science · doi:10.1126/science.1079731 · Cited by 719
THE USE OF 2 H, 13 C, 15 N MULTIDIMENSIONAL NMR GTO STUDY THE STRUCTURE AND DYNAMICS OF PROTEINS
Gardner, K. H., & Kay, L. E. (1998) · Annual Review of Biophysics and Biomolecular Structure · doi:10.1146/annurev.biophys.27.1.357 · Cited by 600
Two-State Allosteric Behavior in a Single-Domain Signaling Protein
Volkman, B. F., Lipson, D., Wemmer, D. E., & Kern, D. (2001) · Science · doi:10.1126/science.291.5512.2429 · Cited by 594
Fang, G., Yu, H., & Kirschner, M. W. (1998) · Genes & Development · doi:10.1101/gad.12.12.1871 · Cited by 594
Self-citationStructural basis of latency in plasminogen activator inhibitor-1
Mottonen, J. M., Strand, A., Symersky, J., Sweet, R. M., Danley, D. E., Geoghegan, K. F., Gerard, R. D., & Goldsmith, E. J. (1992) · Nature · doi:10.1038/355270a0 · Cited by 553
Segregating Sister Genomes: The Molecular Biology of Chromosome Separation
Nasmyth, K. (2002) · Science · doi:10.1126/science.1074757 · Cited by 549
The spindle checkpoint: structural insights into dynamic signalling
Musacchio, A., & Hardwick, K. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm929 · Cited by 532
Mad2-Independent Inhibition of APCCdc20 by the Mitotic Checkpoint Protein BubR1
Tang, Z., Bharadwaj, R., Li, B., & Yu, H. (2001) · Developmental Cell · doi:10.1016/s1534-5807(01)00019-3 · Cited by 411
Self-citationRegulation of APC-Cdc20 by the spindle checkpoint.
Yu, H.-T. (2002) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(02)00382-4 · Cited by 379
Self-citationInsect cells as hosts for the expression of recombinant glycoproteins
Altmann, F., Staudacher, E., Wilson, I. B. H., & März, L. (1999) · Glycoconjugate Journal · doi:10.1023/a:1026488408951 · Cited by 346
Activation of the Budding Yeast Spindle Assembly Checkpoint Without Mitotic Spindle Disruption
Hardwick, K., Weiss, E. L., Luca, F. C., Winey, M., & Murray, A. W. (1996) · Science · doi:10.1126/science.273.5277.953 · Cited by 339
Checkpoint Protein BubR1 Acts Synergistically with Mad2 to Inhibit Anaphase-promoting Complex
Fang, G. (2002) · Molecular Biology of the Cell · doi:10.1091/mbc.01-09-0437 · Cited by 338
Howell, B. J., Hoffman, D. B., Fang, G., Murray, A. W., & Salmon, E. D. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.150.6.1233 · Cited by 327
Sironi, L., Mapelli, M., Knapp, S., Antoni, A. D., Jeang, K., & Musacchio, A. (2002) · The EMBO Journal · doi:10.1093/emboj/21.10.2496 · Cited by 310
Luo, X., Tang, Z., Rizo, J., & Yu, H. (2002) · Molecular Cell · doi:10.1016/s1097-2765(01)00435-x · Cited by 299
Self-citationShah, J. V., & Cleveland, D. W. (2000) · Cell · doi:10.1016/s0092-8674(00)00202-6 · Cited by 276
Structure of the Mad2 spindle assembly checkpoint protein and its interaction with Cdc20.
Yu, H., Wagner, G., Luo, X., Fang, G., Coldiron, M., Lin, Y., & Kirschner, M. W. (2000) · Nature Structural Biology · doi:10.1038/73338 · Cited by 197
Self-citationChen, R. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200204048 · Cited by 192
Chen, R., Brady, D. M., Smith, D. L., Murray, A. W., & Hardwick, K. (1999) · Molecular Biology of the Cell · doi:10.1091/mbc.10.8.2607 · Cited by 177
Identification of a MAD2‐binding protein, CMT2, and its role in mitosis
Habu, T., Kim, S. H., Weinstein, J., & Matsumoto, T. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf659 · Cited by 157
Self-citationMad2 binding to Mad1 and Cdc20, rather than oligomerization, is required for the spindle checkpoint
Sironi, L., Melixetian, M. B., Faretta, M., Prosperini, E., Helin, K., & Musacchio, A. (2001) · The EMBO Journal · doi:10.1093/emboj/20.22.6371 · Cited by 154
Millband, D. N., & Hardwick, K. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.8.2728-2742.2002 · Cited by 141
Spindle Checkpoint Requires Mad1-bound and Mad1-free Mad2
Chung, E., & Chen, R. (2002) · Molecular Biology of the Cell · doi:10.1091/mbc.02-01-0003 · Cited by 130
NMR structure determination of proteins and protein complexes larger than 20 kDa
Clore, G. M., & Gronenborn, A. M. (1998) · Current Opinion in Chemical Biology · doi:10.1016/s1367-5931(98)80084-7 · Cited by 128
The Domain-Swapped Dimer of Cyanovirin-N Is in a Metastable Folded State
Barrientos, L. G., Louis, J. M., Botos, I., Mori, T., Han, Z., O’Keefe, B. R., Boyd, M. R., Wlodawer, A., & Gronenborn, A. M. (2002) · Structure · doi:10.1016/s0969-2126(02)00758-x · Cited by 125
Structural Basis of SNT PTB Domain Interactions with Distinct Neurotrophic Receptors
Dhalluin, C., Yan, K. S., Plotnikova, O., Lee, K., Zeng, L., Kuti, M., Mujtaba, S., Goldfarb, M. P., & Zhou, M.-M. (2000) · Molecular Cell · doi:10.1016/s1097-2765(05)00087-0 · Cited by 107
Mad2 phosphorylation regulates its association with Mad1 and the APC/C
Wassmann, K., Liberal, V., & Benezra, R. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg071 · Cited by 105
Self-citationSerpins and other covalent protease inhibitors
Ye, S. (2001) · Current Opinion in Structural Biology · doi:10.1016/s0959-440x(01)00275-5 · Cited by 102
Structure of α-lytic protease complexed with its pro region
Sauter, N. K., Mau, T., Rader, S. D., & Agard, D. A. (1998) · Nature Structural Biology · doi:10.1038/2919 · Cited by 67
Phosphorylation of Human MAD1 by the BUB1 Kinasein Vitro
Seeley, T. W., Wang, L., & Zhen, J. Y. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.0514 · Cited by 47
Inducing precocious anaphase in cultured mammalian cells
Canman, J. C., Salmon, E. D., & Fang, G. (2002) · Cell Motility and the Cytoskeleton · doi:10.1002/cm.10032 · Cited by 40
Crystal structure of the yeast cell-cycle control protein, p13suc1, in a strand-exchanged dimer
Bernstein, N. K., Bateman, K., Chernaia, M. M., Michalak, M., & James, M. N. G. (1996) · Structure · doi:10.1016/s0969-2126(96)00034-2 · Cited by 25
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On the road to cancer: aneuploidy and the mitotic checkpoint
Kops, G. J. P. L., Weaver, B. A. A., & Cleveland, D. W. (2005) · Nature reviews. Cancer · doi:10.1038/nrc1714 · Cited by 1,201
The molecular biology of spindle assembly checkpoint signaling dynamics.
Musacchio, A. (2015) · Current Biology · doi:10.1016/j.cub.2015.08.051 · Cited by 778
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Metadata
- Authors
- Luo, X., Tang, Z., Xia, G., Wassmann, K., Matsumoto, T., Rizo, J., & Yu, H.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Centre National de la Recherche Scientifique (FR)
- Kyoto University (JP)
- Corresponding author
- Rizo, Josep
- Yu, Hongtao
- Venue
- Nature Structural & Molecular Biology
- Published
- 2004-03-14
- Volume
- 11
- Issue
- 4
- Pages
- 338-345
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- OpenAlex
- W2112512547
- Cited by
- 297
- References
- 42
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 10 · 2023: 16 · 2022: 14 · 2021: 11 · 2020: 12 · 2019: 6 · 2018: 18 · 2017: 15 · 2016: 16 · 2015: 17 · 2014: 17 · 2013: 15 · 2012: 9
- FWCI
- 5.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Structural & Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- Mad2, spindle assembly checkpoint, conformational equilibrium, protein folding, CDC20, Mad1, mitosis, chromosome segregation fidelity, NMR structure
- MeSH terms
- Calcium-Binding Proteins, Cloning, Molecular, HeLa Cells, Humans, Spindle Apparatus, Magnetic Resonance Spectroscopy, Protein Conformation, Recombinant Proteins, Repressor Proteins, Transfection, Restriction Mapping, Cyclins, Protein Folding, Cell Cycle Proteins, Cdc20 Proteins, Mad2 Proteins
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