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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/