دورية أكاديمية
p31comet blocks Mad2 activation through structural mimicry.
| العنوان: | p31comet blocks Mad2 activation through structural mimicry. |
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| المؤلفون: | Yang M; Department of Pharmacology, The University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390, USA., Li B, Tomchick DR, Machius M, Rizo J, Yu H, Luo X |
| المصدر: | Cell [Cell] 2007 Nov 16; Vol. 131 (4), pp. 744-55. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 0413066 Publication Model: Print Cited Medium: Print ISSN: 0092-8674 (Print) Linking ISSN: 00928674 NLM ISO Abbreviation: Cell Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Cambridge, Ma : Cell Press Original Publication: Cambridge, MIT Press. |
| مواضيع طبية MeSH: | Molecular Mimicry* , Protein Structure, Tertiary*, Adaptor Proteins, Signal Transducing/*chemistry , Adaptor Proteins, Signal Transducing/*metabolism , Calcium-Binding Proteins/*chemistry , Calcium-Binding Proteins/*metabolism , Cell Cycle Proteins/*chemistry , Cell Cycle Proteins/*metabolism , Nuclear Proteins/*chemistry , Nuclear Proteins/*metabolism , Repressor Proteins/*chemistry , Repressor Proteins/*metabolism, Adaptor Proteins, Signal Transducing/genetics ; Allosteric Regulation ; Amino Acid Sequence ; Animals ; Calcium-Binding Proteins/genetics ; Cell Cycle/physiology ; Cell Cycle Proteins/genetics ; Cell Line ; Crystallography, X-Ray ; Humans ; Mad2 Proteins ; Models, Molecular ; Molecular Sequence Data ; Multiprotein Complexes/chemistry ; Multiprotein Complexes/metabolism ; Nocodazole/metabolism ; Nuclear Proteins/genetics ; Protein Binding ; Protein Structure, Secondary ; Repressor Proteins/genetics ; Sequence Alignment ; Tubulin Modulators/metabolism |
| مستخلص: | The status of spindle checkpoint signaling depends on the balance of two opposing dynamic processes that regulate the highly unusual two-state behavior of Mad2. In mitosis, a Mad1-Mad2 core complex recruits cytosolic Mad2 to kinetochores through Mad2 dimerization and converts Mad2 to a conformer amenable to Cdc20 binding, thereby facilitating checkpoint activation. p31(comet) inactivates the checkpoint through binding to Mad1- or Cdc20-bound Mad2, thereby preventing Mad2 activation and promoting the dissociation of the Mad2-Cdc20 complex. Here, we report the crystal structure of the Mad2-p31(comet) complex. The C-terminal region of Mad2 that undergoes rearrangement in different Mad2 conformers is a major structural determinant for p31(comet) binding, explaining the specificity of p31(comet) toward Mad1- or Cdc20-bound Mad2. p31(comet) adopts a fold strikingly similar to that of Mad2 and binds at the dimerization interface of Mad2. Thus, p31(comet) exploits the two-state behavior of Mad2 to block its activation by acting as an "anti-Mad2." |
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| معلومات مُعتمدة: | K01 CA100292 United States CA NCI NIH HHS; K01 CA100292-05 United States CA NCI NIH HHS |
| سلسلة جزيئية: | PDB 2QYF |
| المشرفين على المادة: | 0 (Adaptor Proteins, Signal Transducing) 0 (Calcium-Binding Proteins) 0 (Cell Cycle Proteins) 0 (MAD2L1 protein, human) 0 (MAD2L1BP protein, human) 0 (Mad2 Proteins) 0 (Multiprotein Complexes) 0 (Nuclear Proteins) 0 (Repressor Proteins) 0 (Tubulin Modulators) SH1WY3R615 (Nocodazole) |
| تواريخ الأحداث: | Date Created: 20071121 Date Completed: 20080225 Latest Revision: 20211020 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC2144745 |
| DOI: | 10.1016/j.cell.2007.08.048 |
| PMID: | 18022368 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 0092-8674 |
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| DOI: | 10.1016/j.cell.2007.08.048 |