3k0h Citations

Comparison of the structures and peptide binding specificities of the BRCT domains of MDC1 and BRCA1.

Structure 18 167-76 (2010)
Related entries: 3k05, 3k0k, 3k15, 3k16

Cited: 39 times
EuropePMC logo PMID: 20159462

Abstract

The tandem BRCT domains of BRCA1 and MDC1 facilitate protein signaling at DNA damage foci through specific interactions with serine-phosphorylated protein partners. The MDC1 BRCT binds pSer-Gln-Glu-Tyr-COO(-) at the C terminus of the histone variant gammaH2AX via direct recognition of the C-terminal carboxylate, while BRCA1 recognizes pSer-X-X-Phe motifs either at C-terminal or internal sites within target proteins. Using fluorescence polarization binding assays, we show that while both BRCTs prefer a free main chain carboxylate at the +3 position, this preference is much more pronounced in MDC1. Crystal structures of BRCA1 and MDC1 bound to tetrapeptide substrates reveal differences in the environment of conserved arginines (Arg1699 in BRCA1 and Arg1933 in MDC1) that determine the relative affinity for peptides with -COO(-) versus -CO-NH(2) termini. A mutation in MDC1 that induces a more BRCA1-like conformation relaxes the binding specificity, allowing the mutant to bind phosphopeptides lacking a -COO(-) terminus.

Reviews - 3k0h mentioned but not cited (2)

  1. Phosphopeptide interactions with BRCA1 BRCT domains: More than just a motif. Wu Q, Jubb H, Blundell TL. Prog. Biophys. Mol. Biol. 117 143-148 (2015)
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Reviews citing this publication (6)

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  21. Targeting Phosphopeptide Recognition by the Human BRCA1 Tandem BRCT Domain to Interrupt BRCA1-Dependent Signaling. Periasamy J, Kurdekar V, Jasti S, Nijaguna MB, Boggaram S, Hurakadli MA, Raina D, Kurup LM, Chintha C, Manjunath K, Goyal A, Sadasivam G, Bharatham K, Padigaru M, Potluri V, Venkitaraman AR. Cell Chem Biol 25 677-690.e12 (2018)
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