2i3t
Bub3 complex with Mad3 (BubR1) GLEBS motif
Structural highlights
FunctionBUB3_YEAST Required for cell cycle arrest in response to loss of microtubule function. Component of the spindle assembly checkpoint which is a feedback control that prevents cells with incompletely assembled spindles from leaving mitosis. Component of the mitotic checkpoint complex (MCC) which inhibits the ubiquitin ligase activity of the anaphase promoting complex/cyclosome (APC/C) by preventing its activation by CDC20. The formation of a MAD1-BUB1-BUB3 complex seems to be required for the spindle checkpoint mechanism.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe Mad3/BubR1, Mad2, Bub1, and Bub3 proteins are gatekeepers for the transition from metaphase to anaphase. Mad3 from Saccharomyces cerevisiae has homology to Bub1 but lacks a corresponding C-terminal kinase domain. Mad3 forms a stable heterodimer with Bub3. Negative-stain electron microscopy shows that Mad3 is an extended molecule (approximately 200 A long), whereas Bub3 is globular. The Gle2-binding-sequence (GLEBS) motifs found in Mad3 and Bub1 are necessary and sufficient for interaction with Bub3. The calorimetrically determined dissociation constants for GLEBS-motif peptides and Bub3 are approximately 5 microM. Crystal structures of these peptides with Bub3 show that the interactions for Mad3 and Bub1 are similar and mutually exclusive. In both structures, the GLEBS peptide snakes along the top surface of the beta-propeller, forming an extensive interface. Mutations in either protein that disrupt the interface cause checkpoint deficiency and chromosome instability. We propose that the structure imposed on the GLEBS segment by its association with Bub3 enables recruitment to unattached kinetochores. Structural analysis of Bub3 interactions in the mitotic spindle checkpoint.,Larsen NA, Al-Bassam J, Wei RR, Harrison SC Proc Natl Acad Sci U S A. 2007 Jan 23;104(4):1201-6. Epub 2007 Jan 16. PMID:17227844[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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