{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T04:26:20Z","timestamp":1787286380232,"version":"build-2736575974"},"reference-count":30,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001824","name":"Grant Agency of the Czech Republic","doi-asserted-by":"crossref","award":["22-02610K"],"award-info":[{"award-number":["22-02610K"]}],"id":[{"id":"10.13039\/501100001824","id-type":"DOI","asserted-by":"crossref"}]},{"award":["22-02610K"],"award-info":[{"award-number":["22-02610K"]}],"id":[{"id":"https:\/\/ror.org\/01pv73b02","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The bromodomain adjacent to zinc finger (BAZ) family protein TIP5 (transcription termination factor I (TTF-I)\/interacting protein 5) contains a plant homeodomain (PHD) zinc finger module that recognizes unmodified histone H3 lysine 4. This study demonstrates that the immobilized PHD domain recruits the histone octamer complex. Depletion of zinc cations from the finger or disruption via mutagenesis completely abolished this interaction. Interestingly, the binding ability of the depleted protein was partially recovered under high concentrations of KCl. Extending the PHD domain with a PHD-bromodomain (BRD) interdomain linker led to a substantial increase in binding affinity, with the magnitude progressively dependent on the linker length. To gain insight into these preferential binding interfaces, AlphaFold 3 structure predictions were performed. Within the histone octamer complex, histone H3 was identified as a primary, but not sole, binding partner for TIP5 partial proteins. An increase in predicted total van der Waals interactions correlated with the presence of the linker and its extension; however, an anomaly stemming from the calculated stickiness of the short linker version was encountered. Increased hydrogen-bonding in models with the short linker mirrored the observed affinity. Conversely, the long linker reduced predicted hydrogen (H)-bonds below that for the PHD alone. Finally, structural analysis of the disrupted zinc finger motif revealed the fewest hydrogen bonds.<\/jats:p>","DOI":"10.3390\/biom16081209","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T07:58:23Z","timestamp":1787126303000},"page":"1209","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An Intact PHD Finger and PHD-BRD Interdomain Linker Are Crucial for Binding of the Chromatin Remodeler Factor TIP5 to the Histone Octamer"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1993-4260","authenticated-orcid":false,"given":"Pavel","family":"\u010cabart","sequence":"first","affiliation":[{"name":"Department of Cell Nucleus Plasticity, Institute of Experimental Medicine of the Czech Academy of Sciences (IEM CAS), 142 00 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4892","DOI":"10.1093\/emboj\/20.17.4892","article-title":"NoRC\u2014A novel member of mammalian ISWI-containing chromatin remodeling machines","volume":"20","author":"Strohner","year":"2001","journal-title":"EMBO J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1038\/311532a0","article-title":"Structure of the nucleosome core particle at 7 A resolution","volume":"311","author":"Richmond","year":"1984","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/38444","article-title":"Crystal structure of the nucleosome core particle at 2.8 A resolution","volume":"389","author":"Luger","year":"1997","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.str.2014.10.017","article-title":"Molecular basis of histone tail recognition by human TIP5 PHD finger and bromodomain of the chromatin remodeling complex NoRC","volume":"23","author":"Tallant","year":"2015","journal-title":"Structure"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4029","DOI":"10.1038\/sj.emboj.7600382","article-title":"ACF1 improves the effectiveness of nucleosome mobilization by ISWI through PHD-histone contacts","volume":"23","author":"Eberharter","year":"2004","journal-title":"EMBO J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"17643","DOI":"10.1074\/jbc.M117.801464","article-title":"A histone-mimicking interdomain linker in a multidomain protein modulates multivalent histone binding","volume":"292","author":"Kostrhon","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.bbaexp.2003.10.010","article-title":"Mi-2\/NuRD: Multiple complexes for many purposes","volume":"1677","author":"Bowen","year":"2004","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1038\/s41467-017-01598-x","article-title":"Accessibility of the histone H3 tail in the nucleosome for binding of paired readers","volume":"8","author":"Gatchalian","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"ref_10","unstructured":"Strohner, R. (2004). NoRC, A Novel Chromatin Remodeling Complex Involved In Ribosomal RNA Gene Silencing. [Ph.D. Thesis, LMU]."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.ab.2012.05.006","article-title":"Polycistronic coexpression and nondenaturing purification of histone octamers","volume":"427","author":"Shim","year":"2012","journal-title":"Anal. Biochem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1002\/pro.3943","article-title":"UCSF ChimeraX: Structure visualization for researchers, educators, and developers","volume":"30","author":"Pettersen","year":"2021","journal-title":"Protein Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4014","DOI":"10.3390\/ijms11104014","article-title":"Stability and folding behavior analysis of zinc-finger using simple models","volume":"11","author":"Chang","year":"2010","journal-title":"Int. J. Mol. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"14206","DOI":"10.1021\/bi701645g","article-title":"Ionic-strength-dependent effects in protein folding: Analysis of rate equilibrium free-energy relationships and their interpretation","volume":"46","author":"Song","year":"2007","journal-title":"Biochemistry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1002\/prot.20264","article-title":"Scoring function for automated assessment of protein structure template quality","volume":"57","author":"Zhang","year":"2004","journal-title":"Proteins"},{"key":"ref_16","unstructured":"Dunbrack, R.L. (2025). Res ipSAE loquunt: What\u2019s wrong with AlphaFold\u2019s ipTM score and how to fix it. bioRxiv."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4632","DOI":"10.1093\/emboj\/cdf460","article-title":"The chromatin remodeling complex NoRC targets HDAC1 to the ribosomal gene promoter and represses RNA polymerase I transcription","volume":"21","author":"Zhou","year":"2002","journal-title":"EMBO J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"164","DOI":"10.6026\/97320630013164","article-title":"Protein-protein interfaces are vdW dominant with selective H-bonds and (or) electrostatics towards broad functional specificity","volume":"13","author":"Nilofer","year":"2017","journal-title":"Bioinformation"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1038\/256705a0","article-title":"Principles of protein-protein recognition","volume":"256","author":"Chothia","year":"1975","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1002\/pro.5560010117","article-title":"Calculation of the free energy of association for protein complexes","volume":"1","author":"Horton","year":"1992","journal-title":"Protein Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1002\/pro.2230","article-title":"Protein-protein interactions: General trends in the relationship between binding affinity and interfacial buried surface area","volume":"22","author":"Chen","year":"2013","journal-title":"Protein Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"12087","DOI":"10.1038\/s41598-022-16338-5","article-title":"Spatial organization of hydrophobic and charged residues affects protein thermal stability and binding affinity","volume":"12","author":"Desantis","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s12551-024-01199-1","article-title":"Chromatin remodelers: A concise introduction for biophysicists","volume":"16","author":"Klempahn","year":"2024","journal-title":"Biophys. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5735","DOI":"10.1038\/sj.emboj.7601454","article-title":"NoRC-dependent nucleosome positioning silences rRNA genes","volume":"25","author":"Li","year":"2006","journal-title":"EMBO J."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Manelyte, L., Strohner, R., Gross, T., and Langst, G. (2014). Chromatin targeting signals, nucleosome positioning mechanism and non-coding RNA-mediated regulation of the chromatin remodeling complex NoRC. PLoS Genet., 10.","DOI":"10.1371\/journal.pgen.1004157"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/ng1010","article-title":"The nucleolar remodeling complex NoRC mediates heterochromatin formation and silencing of ribosomal gene transcription","volume":"32","author":"Santoro","year":"2002","journal-title":"Nat. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Levesque, M.G., and Picketts, D.J. (2025). It Takes a Village of Chromatin Remodelers to Regulate rDNA Expression. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26041772"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/sj.emboj.7600492","article-title":"The chromatin remodeling complex NoRC controls replication timing of rRNA genes","volume":"24","author":"Li","year":"2005","journal-title":"EMBO J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/ng.3165","article-title":"BAZ2A (TIP5) is involved in epigenetic alterations in prostate cancer and its overexpression predicts disease recurrence","volume":"47","author":"Gu","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5228","DOI":"10.1038\/s41598-024-56073-7","article-title":"Pan-cancer and multi-omics analyses revealed the diagnostic and prognostic value of BAZ2A in liver cancer","volume":"14","author":"Liu","year":"2024","journal-title":"Sci. Rep."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/8\/1209\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T04:17:23Z","timestamp":1787285843000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/8\/1209"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,19]]},"references-count":30,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["biom16081209"],"URL":"https:\/\/doi.org\/10.3390\/biom16081209","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,19]]}}}