3SHT

Crystal structure of human MCPH1 tandem BRCT domains

Summary for 3SHT

• Entry DOI: 10.2210/pdb3sht/pdb
• Related: 3SHV
• Descriptor: Microcephalin (2 entities in total)
• Functional Keywords: tandem brct domains, cell cycle
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome : Q8NEM0
• Total number of polymer chains: 3
• Total formula weight: 68617.85

Authors

Shao, Z.H.,Li, F.D.,Yan, W. (deposition date: 2011-06-17, release date: 2011-12-28, Last modification date: 2023-11-01)

Primary citation

Shao, Z.H.,Li, F.D.,Sy, S.M.-H.,Yan, W.,Zhang, Z.,Gong, D.,Wen, B.,Huen, M.S.Y.,Gong, Q.,Wu, J.,Shi, Y.
Specific recognition of phosphorylated tail of H2AX by the tandem BRCT domains of MCPH1 revealed by complex structure
J.Struct.Biol., 177:459-468, 2012

PubMed Abstract: MCPH1 is especially important for linking chromatin remodeling to DNA damage response. It contains three BRCT (BRCA1-carboxyl terminal) domains. The N-terminal region directly binds with chromatin remodeling complex SWI-SNF, and the C-terminal BRCT2-BRCT3 domains (tandem BRCT domains) are involved in cellular DNA damage response. The MCPH1 gene associates with evolution of brain size, and its variation can cause primary microcephaly. In this study we solve the crystal structures of MCPH1 natural variant (A761) C-terminal tandem BRCT domains alone as well as in complex with γH2AX tail. Compared with other structures of tandem BRCT domains, the most significant differences lie in phosphopeptide binding pocket. Additionally, fluorescence polarization assays demonstrate that MCPH1 tandem BRCT domains show a binding selectivity on pSer +3 and prefer to bind phosphopeptide with free COOH-terminus. Taken together, our research provides new structural insights into BRCT-phosphopeptide recognition mechanism.

PubMed: 22154951
DOI: 10.1016/j.jsb.2011.11.022

Experimental method

X-RAY DIFFRACTION (1.95 Å)