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Crystal structure of the spindle assembly checkpoint protein Bub3
Nicholas A Larsen1, Stephen C Harrison
1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
Journal of Molecular Biology
|November 17, 2004
Summary
Bub3 protein, crucial for cell cycle control, has a unique beta-propeller structure. This structure reveals conserved surfaces likely mediating interactions with other spindle checkpoint proteins, aiding cell division accuracy.
Area of Science:
- Cell Biology
- Structural Biology
- Molecular Genetics
Background:
- Bub3 is a key component of the spindle assembly checkpoint (SAC).
- The SAC ensures accurate chromosome segregation by delaying cell cycle progression.
- Bub3's role in transmitting the SAC signal is critical for preventing aneuploidy.
Purpose of the Study:
- To elucidate the molecular interactions of Bub3.
- To determine the crystal structure of Saccharomyces cerevisiae Bub3p.
- To identify conserved regions involved in protein-protein interactions within the SAC.
Main Methods:
- X-ray crystallography was used to determine the structure of Bub3p.
- Sequence analysis was performed to compare Bub3 with other WD40 proteins.
- Structural features were analyzed to predict interaction sites.
Main Results:
- The crystal structure of Bub3p was determined at 2.35 A resolution.
- Bub3p exhibits a seven-blade beta-propeller fold, distinct from other WD40 family members.
- Conserved residues on the top face and lateral surface suggest interaction sites for Bub1 and Mad3/BubR1.
Conclusions:
- Bub3 possesses a unique beta-propeller structure facilitating interactions within the spindle assembly checkpoint.
- Conserved surfaces on Bub3 likely mediate binding to Bub1 and Mad3/BubR1.
- Similar conserved surfaces in Rae1 suggest analogous binding mechanisms with Bub1.