4QPM

Structure of Bub1 kinase domain

Summary for 4QPM

• Entry DOI: 10.2210/pdb4qpm/pdb
• Descriptor: Mitotic checkpoint serine/threonine-protein kinase BUB1, ADENOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: transferase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: O43683
• Total number of polymer chains: 2
• Total formula weight: 83313.32

Authors

Lin, Z.H.,Jia, L.Y.,Tomchick, D.R.,Luo, X.L.,Yu, H.T. (deposition date: 2014-06-24, release date: 2014-10-22, Last modification date: 2024-11-06)

Primary citation

Lin, Z.,Jia, L.,Tomchick, D.R.,Luo, X.,Yu, H.
Substrate-Specific Activation of the Mitotic Kinase Bub1 through Intramolecular Autophosphorylation and Kinetochore Targeting.
Structure, 22:1616-1627, 2014

PubMed Abstract: During mitosis of human cells, the kinase Bub1 orchestrates chromosome segregation through phosphorylating histone H2A and the anaphase-promoting complex/cyclosome activator Cdc20. Bub1-mediated H2A-T120 phosphorylation (H2A-pT120) at kinetochores promotes centromeric sister-chromatid cohesion, whereas Cdc20 phosphorylation by Bub1 contributes to spindle checkpoint signaling. Here, we show that phosphorylation at the P+1 substrate-binding loop of human Bub1 enhances its activity toward H2A but has no effect on its activity toward Cdc20. We determine the crystal structure of phosphorylated Bub1. A comparison between structures of phosphorylated and unphosphorylated Bub1 reveals phosphorylation-triggered reorganization of the P+1 loop. This activating phosphorylation of Bub1 is constitutive during the cell cycle. Enrichment of H2A-pT120 at mitotic kinetochores requires kinetochore targeting of Bub1. The P+1 loop phosphorylation of Bub1 appears to occur through intramolecular autophosphorylation. Our study provides structural and functional insights into substrate-specific regulation of a key mitotic kinase and expands the repertoire of kinase activation mechanisms.

PubMed: 25308863
DOI: 10.1016/j.str.2014.08.020

Experimental method

X-RAY DIFFRACTION (2.202 Å)