PROSITE documentation PDOC51489BUB1 N-terminal domain profile
The missegregation of sister chromatids during mitosis results in the loss or gain of chromosomes in daughter cells (aneuploidy). This disastrous outcome is avoided by the mitotic checkpoint for spindle assembly (SAC), which monitors the proper assembly of the mitotic spindle and blocks the onset of anaphase until the kinetochores of all chromosomes receive a bipolar attachment to spindle microtubules. BUB1 and BUB1R (BUB1-related kinase, known as MAD3 in the yeast) are multidomain proteins that play central roles in this process, working together with other kinetochore-bound components including MAD2, BUB3, CDC20, and MPS1. BUB1 acts as an upstream component of the mitotic checkpoint pathway, while BUBR1 is a downstream component that inhibits the regulatory protein CDC20. BUB1 and BUBR1 are highly conserved in eukaryotes and share a common architecture: a conserved N-terminal region, a central non-conserved region that contains the bonding region for other mitotic checkpoint components such as BUB3, and a C-terminal serine/threonine kinase domain (see <PDOC00100>). The BUB1 N-terminal domain mediates the binding of BUB1 and BUBR1 to the mitotic kinetochore protein Blinkin [1,2,3,4].
The BUB1 N-terminal domain is composed of eight α-helices arranged in an anti-parallel fashion reminiscent of a TPR domain (see <PDOC50005>). The central six α-helices fold into three sequential helix-loop-helix units (TPR1-3), with their α-helices forming concave inner and outer surfaces (see <PDB:2WVI>). Each of the helix-loop-helix units ressembles a single TPR repeat. The three TPR units are packed together such that "A" α-helices form the inner surface and "B" α-helices form the outer surface, and the entire structure has a subtle right-handed super-helical twist. The BUB1 structure also contains a short N-terminal α-helix connected by a kinked loop and an extended C-terminal α-helix that mimics an A-type helix but protrudes greater than 20 Angstroms from the molecule. These α-helices are unlikely to form additional TPR motifs in the full-length protein given the hydrophilic nature of their outer edges. The extended C-terminal α-helix ressembles a caping α-helix as observed in numerous TPR domains [3,4].
The profile we developed covers the entire BUB1 N-terminal domain.
Last update:June 2010 / First entry.
-------------------------------------------------------------------------------
PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Bolanos-Garcia V.M. Beaufils S. Renault A. Grossmann J.G. Brewerton S. Lee M. Venkitaraman A. Blundell T.L. |
| Title | The conserved N-terminal region of the mitotic checkpoint protein BUBR1: a putative TPR motif of high surface activity. | |
| Source | Biophys. J. 89:2640-2649(2005). | |
| PubMed ID | 16040755 | |
| DOI | 10.1529/biophysj.105.063511 |
| 2 | Authors | Beaufils S. Grossmann J.G. Renault A. Bolanos-Garcia V.M. |
| Title | Characterization of the tetratricopeptide-containing domain of BUB1, BUBR1, and PP5 proves that domain amphiphilicity over amino acid sequence specificity governs protein adsorption and interfacial activity. | |
| Source | J. Phys. Chem. B 112:7984-7991(2008). | |
| PubMed ID | 18547097 | |
| DOI | 10.1021/jp711222s |
| 3 | Authors | Bolanos-Garcia V.M. Kiyomitsu T. D'Arcy S. Chirgadze D.Y. Grossmann J.G. Matak-Vinkovic D. Venkitaraman A.R. Yanagida M. Robinson C.V. Blundell T.L. |
| Title | The crystal structure of the N-terminal region of BUB1 provides insight into the mechanism of BUB1 recruitment to kinetochores. | |
| Source | Structure 17:105-116(2009). | |
| PubMed ID | 19141287 | |
| DOI | 10.1016/j.str.2008.10.015 |
| 4 | Authors | D'Arcy S. Davies O.R. Blundell T.L. Bolanos-Garcia V.M. |
| Title | Defining the molecular basis of BubR1 kinetochore interactions and APC/C-CDC20 inhibition. | |
| Source | J. Biol. Chem. 285:14764-14776(2010). | |
| PubMed ID | 20220147 | |
| DOI | 10.1074/jbc.M109.082016 |
PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see prosite_license.html.
View entry in original PROSITE document format
View entry in raw text format (no links)