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| Autori principali: | , , , , , , , , , , , , , , , , , , , |
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| Natura: | Artículo científico |
| Lingua: | en |
| Pubblicazione: |
Science (New York, N.Y.)
2025
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| Accesso online: | https://pubmed.ncbi.nlm.nih.gov/40245140/ |
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| author | Chen, Luying Dickerhoff, Jonathan Zheng, Ke-Wei Erramilli, Satchal Feng, Hanqiao Wu, Guanhui Onel, Buket Chen, Yuwei Wang, Kai-Bo Carver, Megan Lin, Clement Sakai, Saburo Wan, Jun Vinson, Charles Hurley, Laurence Kossiakoff, Anthony A Deng, Nanjie Bai, Yawen Noinaj, Nicholas Yang, Danzhou |
| author_facet | Chen, Luying Dickerhoff, Jonathan Zheng, Ke-Wei Erramilli, Satchal Feng, Hanqiao Wu, Guanhui Onel, Buket Chen, Yuwei Wang, Kai-Bo Carver, Megan Lin, Clement Sakai, Saburo Wan, Jun Vinson, Charles Hurley, Laurence Kossiakoff, Anthony A Deng, Nanjie Bai, Yawen Noinaj, Nicholas Yang, Danzhou Chen, Luying Dickerhoff, Jonathan Zheng, Ke-Wei Erramilli, Satchal Feng, Hanqiao Wu, Guanhui Onel, Buket Chen, Yuwei Wang, Kai-Bo Carver, Megan Lin, Clement Sakai, Saburo Wan, Jun Vinson, Charles Hurley, Laurence Kossiakoff, Anthony A Deng, Nanjie Bai, Yawen Noinaj, Nicholas Yang, Danzhou |
| collection | PubMed - marine biology |
| contents | Structural basis for nucleolin recognition of promoter G-quadruplex. Chen, Luying Dickerhoff, Jonathan Zheng, Ke-Wei Erramilli, Satchal Feng, Hanqiao Wu, Guanhui Onel, Buket Chen, Yuwei Wang, Kai-Bo Carver, Megan Lin, Clement Sakai, Saburo Wan, Jun Vinson, Charles Hurley, Laurence Kossiakoff, Anthony A Deng, Nanjie Bai, Yawen Noinaj, Nicholas Yang, Danzhou Humans Crystallography, X-Ray G-Quadruplexes Genes, myc Models, Molecular Nucleolin Potassium Promoter Regions, Genetic Protein Binding Protein Domains Proto-Oncogene Proteins c-myc RNA-Binding Proteins The oncogene promoter G-quadruplex (MycG4) regulates transcription and is a prevalent G4 locus in immortal cells. Nucleolin, a major MycG4-binding protein, exhibits greater affinity for MycG4 than for nucleolin recognition element (NRE) RNA. Nucleolin's four RNA binding domains (RBDs) are essential for high-affinity MycG4 binding. We present the 2.6-angstrom crystal structure of the nucleolin-MycG4 complex, revealing a folded parallel three-tetrad G-quadruplex with two coordinating potassium ions (K), interacting with RBD1, RBD2, and Linker12 through its 6-nucleotide (nt) central loop and 5' flanking region. RBD3 and RBD4 bind MycG4's 1-nt loops as demonstrated by nuclear magnetic resonance (NMR). Cleavage under targets and tagmentation sequencing confirmed nucleolin's binding to MycG4 in cells. Our results revealed a G4 conformation-based recognition by a regulating protein through multivalent interactions, suggesting that G4s are nucleolin's primary cellular substrates, indicating G4 epigenetic transcriptional regulation and helping G4-targeted drug discovery. |
| format | Artículo científico |
| id | pubmed_40245140 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | Science (New York, N.Y.) |
| record_format | pubmed |
| spellingShingle | Structural basis for nucleolin recognition of promoter G-quadruplex. Chen, Luying Dickerhoff, Jonathan Zheng, Ke-Wei Erramilli, Satchal Feng, Hanqiao Wu, Guanhui Onel, Buket Chen, Yuwei Wang, Kai-Bo Carver, Megan Lin, Clement Sakai, Saburo Wan, Jun Vinson, Charles Hurley, Laurence Kossiakoff, Anthony A Deng, Nanjie Bai, Yawen Noinaj, Nicholas Yang, Danzhou Humans Crystallography, X-Ray G-Quadruplexes Genes, myc Models, Molecular Nucleolin Potassium Promoter Regions, Genetic Protein Binding Protein Domains Proto-Oncogene Proteins c-myc RNA-Binding Proteins Structural basis for nucleolin recognition of promoter G-quadruplex. Chen, Luying Dickerhoff, Jonathan Zheng, Ke-Wei Erramilli, Satchal Feng, Hanqiao Wu, Guanhui Onel, Buket Chen, Yuwei Wang, Kai-Bo Carver, Megan Lin, Clement Sakai, Saburo Wan, Jun Vinson, Charles Hurley, Laurence Kossiakoff, Anthony A Deng, Nanjie Bai, Yawen Noinaj, Nicholas Yang, Danzhou Humans Crystallography, X-Ray G-Quadruplexes Genes, myc Models, Molecular Nucleolin Potassium Promoter Regions, Genetic Protein Binding Protein Domains Proto-Oncogene Proteins c-myc RNA-Binding Proteins The oncogene promoter G-quadruplex (MycG4) regulates transcription and is a prevalent G4 locus in immortal cells. Nucleolin, a major MycG4-binding protein, exhibits greater affinity for MycG4 than for nucleolin recognition element (NRE) RNA. Nucleolin's four RNA binding domains (RBDs) are essential for high-affinity MycG4 binding. We present the 2.6-angstrom crystal structure of the nucleolin-MycG4 complex, revealing a folded parallel three-tetrad G-quadruplex with two coordinating potassium ions (K), interacting with RBD1, RBD2, and Linker12 through its 6-nucleotide (nt) central loop and 5' flanking region. RBD3 and RBD4 bind MycG4's 1-nt loops as demonstrated by nuclear magnetic resonance (NMR). Cleavage under targets and tagmentation sequencing confirmed nucleolin's binding to MycG4 in cells. Our results revealed a G4 conformation-based recognition by a regulating protein through multivalent interactions, suggesting that G4s are nucleolin's primary cellular substrates, indicating G4 epigenetic transcriptional regulation and helping G4-targeted drug discovery. |
| title | Structural basis for nucleolin recognition of promoter G-quadruplex. |
| topic | Humans Crystallography, X-Ray G-Quadruplexes Genes, myc Models, Molecular Nucleolin Potassium Promoter Regions, Genetic Protein Binding Protein Domains Proto-Oncogene Proteins c-myc RNA-Binding Proteins |
| url | https://pubmed.ncbi.nlm.nih.gov/40245140/ |