9C0O

Crystal structure of DmCfp1 PHD finger bound to H3K4me3

Summary for 9C0O

• Entry DOI: 10.2210/pdb9c0o/pdb
• Descriptor: CXXC-type zinc finger protein 1, Histone H3.3C, DIMETHYL SULFOXIDE, ... (6 entities in total)
• Functional Keywords: chromatin binding protein, histone h3 reader, metal binding protein
• Biological source: Drosophila melanogaster (fruit fly); More
• Total number of polymer chains: 2
• Total formula weight: 9939.30

Authors

Gregoire, S.,Couture, J.F. (deposition date: 2024-05-27, release date: 2024-07-03, Last modification date: 2024-09-25)

Primary citation

Gregoire, S.,Gregoire, J.,Yang, Y.,Capitani, S.,Joshi, M.,Sarvan, S.,Zaker, A.,Ning, Z.,Figeys, D.,Ulrich, K.,Brunzelle, J.S.,Mer, A.,Couture, J.F.
Structural insights into an atypical histone binding mechanism by a PHD finger.
Structure, 32:1498-, 2024

PubMed Abstract: Complex associating with SET1 (COMPASS) is a histone H3K4 tri-methyltransferase controlled by several regulatory subunits including CXXC zinc finger protein 1 (Cfp1). Prior studies established the structural underpinnings controlling H3K4me3 recognition by the PHD domain of Cfp1's yeast homolog (Spp1). However, metazoans Cfp1 lacks structural elements important for H3K4me3 stabilization in Spp1, suggesting that in metazoans, Cfp1 domain binds H3K4me3 differently. The structure of Cfp1 in complex with H3K4me3 shows unique features such as non-canonical coordination of the first zinc atom and a disulfide bond forcing the reorientation of Cfp1 N-terminus, thereby leading to an atypical H3K4me3 binding pocket. This configuration minimizes Cfp1 reliance on canonical residues important for histone binding functions of other PHD domains. Cancer-related mutations in Cfp1 impair H3K4me3 binding, implying a potential impact on epigenetic signaling. Our work highlights a potential diversification of PHD histone binding modes and the impact of cancer mutations on Cfp1 functions.

PubMed: 39029460
DOI: 10.1016/j.str.2024.06.017

Experimental method

X-RAY DIFFRACTION (1.53 Å)