8sxm | pdb_00008sxm

NMR structure of the ZNF750 zinc finger domain, Z*

spinqualitylabelsall models 8sxm Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8sxm is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR Ligands: ACE, NH2, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease ZN750_HUMAN Seborrhea-like dermatitis with psoriasiform elements. The disease is caused by variants affecting the gene represented in this entry. Function ZN750_HUMAN Transcription factor involved in epidermis differentiation. Required for terminal epidermal differentiation: acts downstream of p63/TP63 and activates expression of late epidermal differentiation genes. Specifically binds to the promoter of KLF4 and promotes its expression. Publication Abstract from PubMed ZNF750 is a nuclear transcription factor that activates skin differentiation and has tumor suppressor roles in several cancers. Unusually, ZNF750 has only a single zinc-finger (ZNF) domain, Z*, with an amino acid sequence that differs markedly from the CCHH family consensus. Because of its sequence differences Z* is classified as degenerate, presumed to have lost the ability to bind the zinc ion required for folding. AlphaFold predicts an irregular structure for Z* with low confidence. Low confidence predictions are often inferred to be intrinsically disordered regions of proteins, which would be the case if Z* did not bind Zn(2+). We use NMR and CD spectroscopy to show that a 25-51 segment of ZNF750 corresponding to the Z* domain, folds into a well-defined antiparallel betabetaalpha tertiary structure, with a pM dissociation constant for Zn(2+) and a thermal stability >80 (o)C. Of three alternative Zn(2+) ligand sets, Z* uses a CCHC rather than the expected CCHH ligating motif. The switch in the last ligand maintains the folding topology and hydrophobic core of the classical ZNF motif. CCHC ZNFs are typically associated with protein-protein interactions, raising the possibility that ZNF750 interacts with DNA through other proteins rather than directly. The structure of Z* provides context for understanding the function of the domain and its cancer-associated mutations. We expect other ZNFs currently classified as degenerate could be CCHC-type structures like Z*. NMR structure verifies the eponymous zinc finger domain of transcription factor ZNF750.,Rua AJ, Whitehead Iii RD, Alexandrescu AT J Struct Biol. 2023 Jul 22:108003. doi: 10.1016/j.jsb.2023.108003. PMID:37487847 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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