6J2P

Crystal structure of Saccharomyces cerevisiae Spp1 in complex with H3K4me3

Summary for 6J2P

• Entry DOI: 10.2210/pdb6j2p/pdb
• Descriptor: COMPASS component SPP1, Histone H3, ZINC ION (3 entities in total)
• Functional Keywords: histone modification recognition, protein binding
• Biological source: Saccharomyces cerevisiae S288c (Baker's yeast); More
• Total number of polymer chains: 8
• Total formula weight: 61045.54

Authors

He, C.,Li, F. (deposition date: 2019-01-02, release date: 2019-09-11)

Primary citation

He, C.,Liu, N.,Xie, D.,Liu, Y.,Xiao, Y.,Li, F.
Structural basis for histone H3K4me3 recognition by the N-terminal domain of the PHD finger protein Spp1.
Biochem.J., 476:1957-1973, 2019

PubMed Abstract: Spp1, a plant homeodomain (PHD) finger containing protein, is a critical subunit of the histone H3K4 methyltransferase complex of proteins associated with Set1 (COMPASS). The chromatin binding affinity of the PHD finger of Spp1 has been proposed to modulate COMPASS activity. During meiosis, Spp1 plays another role in promoting programmed double-strand break (DSB) formation by binding H3K4me3 via its PHD finger and interacting with a DSB protein, Mer2. However, how the Spp1 PHD finger performs site-specific readout of H3K4me3 is still not fully understood. In the present study, we determined the crystal structure of the highly conserved Spp1 N-terminal domain (Sc_Spp1) in complex with the H3K4me3 peptide. The structure shows that Sc_Spp1 comprises a PHD finger responsible for methylated H3K4 recognition and a C3H-type zinc finger necessary to ensure the overall structural stability. Our isothermal titration calorimetry results show that binding of H3K4me3 to Sc_Spp1 is mildly inhibited by H3R2 methylation, weakened by H3T6 phosphorylation, and abrogated by H3T3 phosphorylation. This histone modification cross-talk, which is conserved in the and mammalian orthologs of Sc_Spp1 , can be rationalized structurally and might contribute to the roles of Spp1 in COMPASS activity regulation and meiotic recombination.

PubMed: 31253666
DOI: 10.1042/BCJ20190091

Experimental method

X-RAY DIFFRACTION (2.85 Å)