2vfx

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{{STRUCTURE_2vfx| PDB=2vfx | SCENE= }}
{{STRUCTURE_2vfx| PDB=2vfx | SCENE= }}
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'''STRUCTURE OF THE SYMMETRIC MAD2 DIMER'''
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===STRUCTURE OF THE SYMMETRIC MAD2 DIMER===
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==Overview==
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In response to misaligned sister chromatids during mitosis, the spindle checkpoint protein Mad2 inhibits the anaphase-promoting complex or cyclosome (APC/C) through binding to its mitotic activator Cdc20, thus delaying anaphase onset. Mad1, an upstream regulator of Mad2, forms a tight core complex with Mad2 and facilitates Mad2 binding to Cdc20. In the absence of its binding proteins, free Mad2 has two natively folded conformers, termed N1-Mad2/open-Mad2 (O-Mad2) and N2-Mad2/closed Mad2 (C-Mad2), with C-Mad2 being more active in APC/C(Cdc20) inhibition. Here, we show that whereas O-Mad2 is monomeric, C-Mad2 forms either symmetric C-Mad2-C-Mad2 (C-C) or asymmetric O-Mad2-C-Mad2 (O-C) dimers. We also report the crystal structure of the symmetric C-C Mad2 dimer, revealing the basis for the ability of unliganded C-Mad2, but not O-Mad2 or liganded C-Mad2, to form symmetric dimers. A Mad2 mutant that predominantly forms the C-C dimer is functional in vitro and in living cells. Finally, the Mad1-Mad2 core complex facilitates the conversion of O-Mad2 to C-Mad2 in vitro. Collectively, our results establish the existence of a symmetric Mad2 dimer and provide insights into Mad1-assisted conformational activation of Mad2 in the spindle checkpoint.
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(as it appears on PubMed at http://www.pubmed.gov), where 18318601 is the PubMed ID number.
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{{ABSTRACT_PUBMED_18318601}}
==About this Structure==
==About this Structure==
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[[Category: Nucleus]]
[[Category: Nucleus]]
[[Category: Spindle checkpoint]]
[[Category: Spindle checkpoint]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 18:43:36 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 16:14:47 2008''

Revision as of 13:14, 29 July 2008

Template:STRUCTURE 2vfx

STRUCTURE OF THE SYMMETRIC MAD2 DIMER

Template:ABSTRACT PUBMED 18318601

About this Structure

2VFX is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Insights into Mad2 Regulation in the Spindle Checkpoint Revealed by the Crystal Structure of the Symmetric Mad2 Dimer., Yang M, Li B, Liu CJ, Tomchick DR, Machius M, Rizo J, Yu H, Luo X, PLoS Biol. 2008 Mar 4;6(3):e50. PMID:18318601

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