9xvf | pdb_00009xvf

Crystal structure of NFIA monomer bound to DNA

spinqualitylabelsall models 9xvf, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9xvf is a 4 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.6Å Ligands: 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 I (NFI) transcription factors play essential roles in multiple aspects of nervous system development, including radial glia maturation, neurogenesis, gliogenesis, and brain morphogenesis. Numerous NFI variants have been identified in individuals with neurodevelopmental disorders, yet the molecular basis of their pathogenicity remains unclear. The absence of resolved NFI-DNA complex structures continues to impede mechanistic insights and therapeutic exploration. Here, we define the oligomeric states of NFIA and NFIC, and determine the crystal structures of the NFIC homodimer, as well as the NFIA and NFIC monomers lacking their dimerization region, in complexes with double-stranded DNAs. Structural analysis reveals the molecular mechanism underlying NFI dimerization and recognition of a dyad-symmetric TGGCA(N3)TGCCA sequence motif, and demonstrates that dimerization enhances both DNA-binding affinity and specificity of NFI proteins. The functional importance of key NFI residues and DNA bases involved in the protein-DNA interaction is further validated by mutagenesis and binding assays. Additionally, we systematically evaluate the effects of the neurodevelopmental disorders-associated NFI mutations on DNA binding of NFIA, providing insights into their potential pathogenic mechanisms. Together, our findings elucidate the structural basis of NFI dimerization and dyad-symmetric DNA recognition and highlight pathogenic variants for further mechanistic studies in neurodevelopmental disorders. Biochemical and structural studies of NFIA and NFIC reveal a conserved mechanism for specific DNA recognition and provide insight into potential pathogenicity of disease-associated mutations.,Pan S, Pei W, Zhang J, Min J, Liu K Acta Biochim Biophys Sin (Shanghai). 2025 Dec 18. doi: 10.3724/abbs.2025236. PMID:41408833 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA