{"doi":"10.1093/nar/gkac1274","title":"Allosteric autoregulation of DNA binding via a DNA-mimicking protein domain: a biophysical study of ZNF410–DNA interaction using small angle X-ray scattering","abstract":"ZNF410 is a highly-conserved transcription factor, remarkable in that it recognizes a 15-base pair DNA element but has just a single responsive target gene in mammalian erythroid cells. ZNF410 includes a tandem array of five zinc-fingers (ZFs), surrounded by uncharacterized N- and C-terminal regions. Unexpectedly, full-length ZNF410 has reduced DNA binding affinity, compared to that of the isolated DNA binding ZF array, both in vitro and in cells. AlphaFold predicts a partially-folded N-terminal subdomain that includes a 30-residue long helix, preceded by a hairpin loop rich in acidic (aspartate/glutamate) and serine/threonine residues. This hairpin loop is predicted by AlphaFold to lie against the DNA binding interface of the ZF array. In solution, ZNF410 is a monomer and binds to DNA with 1:1 stoichiometry. Surprisingly, the single best-fit model for the experimental small angle X-ray scattering profile, in the absence of DNA, is the original AlphaFold model with the N-terminal long-helix and the hairpin loop occupying the ZF DNA binding surface. For DNA binding, the hairpin loop presumably must be displaced. After combining biophysical, biochemical, bioinformatic and artificial intelligence-based AlphaFold analyses, we suggest that the hairpin loop mimics the structure and electrostatics of DNA, and provides an additional mechanism, supplementary to sequence specificity, of regulating ZNF410 DNA binding.","journal":"Nucleic Acids Research","year":2023,"id":357263,"datarank":0.3958585994422889,"base_score":2.639057329615259,"endowment":2.639057329615259,"self_citation_contribution":0.3958585994422889,"citation_network_contribution":0.0,"self_endowment_contribution":0.3958585994422889,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9585,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":362021,"name":"Ren Ren","orcid":"0000-0001-8288-8012","position":1,"is_corresponding":false},{"id":260633,"name":"Michal Hammel","orcid":"0000-0002-5610-9289","position":2,"is_corresponding":false},{"id":356766,"name":"J.R. Horton","orcid":"0000-0001-9749-8068","position":3,"is_corresponding":false},{"id":647920,"name":"Jie Yang","orcid":"0000-0003-2241-5066","position":4,"is_corresponding":false},{"id":1106729,"name":"Yu Cao","orcid":"0000-0003-4368-7757","position":5,"is_corresponding":false},{"id":281240,"name":"Chenxi He","orcid":"0000-0001-9421-6707","position":6,"is_corresponding":false},{"id":281251,"name":"Fei Lan","orcid":"0000-0002-8559-7146","position":7,"is_corresponding":false},{"id":376401,"name":"Xianjiang Lan","orcid":"0000-0001-8208-2916","position":8,"is_corresponding":false},{"id":90395,"name":"Gerd A. Blobel","orcid":"0000-0002-0714-9612","position":9,"is_corresponding":false},{"id":356768,"name":"Robert Blumenthal","orcid":"0000-0002-0873-0724","position":10,"is_corresponding":false},{"id":378259,"name":"Xing Zhang","orcid":"0000-0002-6776-326X","position":11,"is_corresponding":false},{"id":356553,"name":"Xiaodong Cheng","orcid":"0000-0002-6967-6362","position":12,"is_corresponding":false},{"id":362020,"name":"Gundeep Kaur","orcid":"0000-0003-3481-9527","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:13:34.795336Z","pmid":"36660822","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}