Structural Basis for the Recognition of Phosphorylated Histone H3 by the Survivin Subunit of the Chromosomal Passenger Complex

Jeyaprakash Arulanandam, Claire Basquin, Uma Jayachandran, Elena Conti

Research output: Contribution to journalArticlepeer-review

Abstract

Localization of the chromosomal passenger complex (CPC) at centromeres during early mitosis is essential for accurate chromosome segregation and is dependent on the phosphorylation of histone H3. We report the 2.7 angstrom resolution structure of the CPC subunit Survivin bound to the N-terminal tail of histone H3 carrying the Thr3 phosphorylation mark (Thr3ph). The BIR domain of Survivin recognizes the Ala1-Arg2-Thr3ph-Lys4 sequence, decoding the modification state and the free N terminus of histone H3 by a strategy similar to that used by PHD fingers. The structural analysis permitted the identification of putative Survivin-binding epitopes in other mitotic proteins, including human Shugoshin 1. Using biophysical and structural data, we show that a phospho-mimic N-terminal sequence such as that of hSgo1 (Ala1-Lys2-Glu3-Arg4) contains the specificity determinants to bind Survivin. Our findings suggest that the CPC engages in mutually exclusive interactions with other constituents of the mitotic machinery and a histone mark in chromatin.

Original languageEnglish
Pages (from-to)1625-1634
Number of pages10
JournalStructure
Volume19
Issue number11
Early online date27 Oct 2011
DOIs
Publication statusPublished - 9 Nov 2011

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