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

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 Å 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.

Structural basis for histone mimicry and hijacking of host proteins by influenza virus protein NS1

“…Consistently, neither ING4 nor SGF29 showed detectable binding to a corresponding NS1 peptide (Table 1). Another example is Survivin, which specifically recognizes phosphorylated H3T3 and also requires the free N-terminal amine of H3 for interaction 16 . Why is CHD1 able to recognize the methylated 226 ARSK 229 motif of NS1 in a C-terminal context?…”

Piperine derivatives as potential inhibitors of Survivin: An in silico molecular docking

“…It has been shown that binding of Survivin to the phosphorylated form of the histone H3 N-terminus (H3-T3ph) is essential in CPC formation [21]. Survivin has an available binding site on its BIR domain to identify H3-T3ph.…”

Protein and DNA Modifications: Evolutionary Imprints of Bacterial Biochemical Diversification and Geochemistry on the Provenance of Eukaryotic Epigenetics

“…2J) are traceable to the LECA (Lloyd et al 2009;Zippo et al 2009;Garcia-Alai et al 2010;Singh et al 2012). However, the histone H3T3-binding BIR domain appears to be a later innovation in eukaryotic evolution, probably emerging concomitantly with haspin-like kinases that modify the position recognized by them (Jeyaprakash et al 2011).…”