9lc2

Crystal Structure of NFIA in Complex with DNA Containing the TGGCA(N3)TGCCA Motif

spinqualitylabelsall models 9lc2, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9lc2 is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.7Å Ligands: EDO, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease NFIA_HUMAN 1p31p32 microdeletion syndrome. The disease is caused by variants affecting the gene represented in this entry. Function NFIA_HUMAN Recognizes and binds the palindromic sequence 5'-TTGGCNNNNNGCCAA-3' present in viral and cellular promoters and in the origin of replication of adenovirus type 2. These proteins are individually capable of activating transcription and replication. Publication Abstract from PubMed Nuclear Factor IA, a member of the long-studied Nuclear Factor I family of DNA-binding proteins, plays pivotal roles in development and metabolism. Dysregulation or loss of Nuclear Factor IA is associated with severe neurological defects in humans and disruptions in fatty acid metabolism linked to conditions such as osteoarthritis. Despite extensive study, the DNA recognition mechanism of Nuclear Factor I family proteins remains unresolved. Previous studies have proposed that these proteins dimerize via their DNA-binding domains to bind TGGCA-containing dyad sequences. In this study, we demonstrate that both full-length Nuclear Factor IA and its isolated DNA-binding domain are monomeric in solution, challenging dimer models. Genome-wide ChIP-Seq analysis shows TGGCA half-sites are enriched among Nuclear Factor IA binding motifs. We determine Nuclear Factor IA's crystal and solution structures bound to half-site and dyad-symmetric DNA motifs, providing a structural basis for its monomeric DNA recognition. Furthermore, functional binding assays show that key residues in Nuclear Factor IA, which facilitate base-specific interactions, are critical for DNA sequence recognition and binding. These findings establish the DNA-binding mechanism of Nuclear Factor IA and provide a detailed molecular framework for understanding the functions of this classic transcription factor family. Structural basis for genome-wide site-specific DNA recognition by Nuclear Factor IA.,Zhu C, Xiao D, Luo Z, Zhang J, Liu S, Wang Y, Chen X, Xiao H, Li X, Tang J, Fang X, Shen J, Song H Nat Commun. 2025 Dec 15. doi: 10.1038/s41467-025-67641-4. PMID:41398321 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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