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Publication Abstract from PubMed

The PHD finger-containing VARIANT IN METHYLATION/ORTHRUS (VIM/ORTH) family of proteins in Arabidopsis consists of functional homologues of mammalian UHRF1 and is required for the maintenance of DNA methylation. Comparison of the sequence with those of other PHD fingers implied that VIM1 and VIM3 PHD could recognize lysine 4 of histone H3 (H3K4) through interactions mediated by a conserved aspartic acid. However, our calorimetric and modified histone peptide array binding studies suggested that neither H3K4 nor other histone marks are recognized by VIM1 and VIM3 PHD fingers. Here, we report a 2.6 A resolution crystal structure of the VIM1 PHD finger and demonstrate significant structural changes in the putative H3 recognition segments in contrast to canonical H3K4 binding PHD fingers. These changes include (i) the H3A1 binding region, (ii) strand beta1 that forms an intermolecular beta-sheet with the H3 peptide, and (iii) an aspartate-containing motif involved in salt bridge interaction with H3K4, which together appear to abrogate recognition of H3K4 by the VIM1 PHD finger. To understand the significance of the altered structural features in the VIM1 PHD that might prevent histone H3 recognition, we modeled a chimeric VIM1 PHD (chmVIM1 PHD) by grafting the peptide binding structural features of the BHC80 PHD onto the VIM1 PHD. Molecular dynamics simulation and metadynamics analyses revealed that the chmVIM1 PHD-H3 complex is stable and also showed a network of intermolecular interactions similar to those of the BHC80 PHD-H3 complex. Collectively, this study reveals that subtle structural changes in the peptide binding region of the VIM1 PHD abrogate histone H3 recognition.

Helical and beta-Turn Conformations in the Peptide Recognition Regions of the VIM1 PHD Finger Abrogate H3K4 Peptide Recognition.,Abhishek S, Deeksha W, Rajakumara E Biochemistry. 2021 Aug 18. doi: 10.1021/acs.biochem.1c00191. PMID:34404204^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.