{"doi":"10.1039/c2mb05354c","title":"Forced homodimerization of the c-Fos leucine zipper in designed bHLHZ-like hybrid proteins MaxbHLH-Fos and ArntbHLH-Fos","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Although the c-Fos leucine zipper (LZ) does not form a homodimer in its native basic region/leucine zipper (bZIP) structure, we found that it is capable of homodimerization and promoting protein folding in engineered basic region/helix–loop–helix/leucine zipper (bHLHZ) hybrid proteins MaxbHLH-Fos and ArntbHLH-Fos, in which the bHLH subdomains of Max and Arnt are fused to the c-Fos LZ. By using the in vivo yeast one-hybrid system and in vitro circular dichroism and quantitative fluorescence anisotropy, we demonstrated that attachment of the c-Fos LZ to the otherwise unstructured MaxbHLH resulted in a hybrid bHLHZ-like protein now competent for homodimerization and DNA binding at the cognate E-box site, CACGTG. In ArntbHLH-Fos, the c-Fos LZ promoted proper folding of the HLH structure, although unlike MaxbHLH, ArntbHLH alone is capable of homodimerization and DNA binding. In addition, by comparing the E-box binding and secondary structures of MaxbHLH-Fos and two derivatives containing targeted mutations in the c-Fos LZ, we found that cooperative communication exists between the bHLH and LZ: proper folding of the four-helix bundle in the HLH region could be induced by the c-Fos LZ, and the HLH dimerization region could force homodimerization of the c-Fos LZ. These results demonstrate that although intrinsically unfavorable, the c-Fos LZ can homodimerize, demonstrating that the same c-Fos LZ element can yield orthogonal differences in structure and/or DNA-binding function within different transcription factor families, including the bZIP and bHLHZ.</jats:p>\n                  <jats:p/>","journal":"Molecular BioSystems","year":2012,"id":15651,"datarank":0.3829299218384227,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.05334623523798977,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.05334623523798977,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":3,"citers_with_citation_signal":2,"citers_with_endowment":2,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":118683,"name":"Antonia T De Jong","orcid":null,"position":1,"is_corresponding":false},{"id":118684,"name":"Jumi A Shin","orcid":null,"position":2,"is_corresponding":false},{"id":105505,"name":"Gang Chen","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"22301802","pmcid":null,"openalex_id":"https://openalex.org/W1972621583","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM069041","title":null}],"total_grants":1,"fwci":0.1343,"citation_percentile":0.50821028,"influential_citations":0,"citation_trend":[{"year":2014,"count":1},{"year":2017,"count":1},{"year":2019,"count":1},{"year":2020,"count":2},{"year":2024,"count":1},{"year":2025,"count":2}],"oa_status":"closed","license":"https://academic.oup.com/pages/standard-publication-reuse-rights","oa_locations":[{"url":"https://academic.oup.com/molecular-omics/article-pdf/8/4/1286/66162906/c2mb05354c.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1039/c2mb05354c","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/22301802","host_type":"repository"}],"fields_of_study":["RNA and protein synthesis mechanisms","Transgenic Plants and Applications","Plant Virus Research Studies","Medicine","Biology","Chemistry","Materials Science","Amino Acid Sequence","Circular Dichroism","DNA-Binding Proteins","Dimerization","E-Box Elements","Helix-Turn-Helix Motifs","Leucine Zippers","Models, Molecular","Molecular Sequence Data","Protein Folding","Protein Multimerization","Protein Structure, Secondary","Proto-Oncogene Proteins c-fos","Recombinant Fusion Proteins"],"mesh_terms":["Amino Acid Sequence","Circular Dichroism","DNA-Binding Proteins","Models, Molecular","Molecular Sequence Data","Recombinant Fusion Proteins","Leucine Zippers","Proto-Oncogene Proteins c-fos","Protein Structure, Secondary","Protein Folding","Helix-Turn-Helix Motifs","Dimerization","E-Box Elements","Protein Multimerization"],"keywords":["Leucine zipper","bZIP domain","Zipper","Basic helix-loop-helix","Transcription factor","Basic helix-loop-helix leucine zipper transcription factors","Chemistry","DNA","Coiled coil","DNA-binding protein","Cell biology","Biochemistry","Biophysics","Biology","Gene"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-01T18:29:50.933693Z","pmid":null,"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":[]}