2ko0

Solution structure of the THAP zinc finger of THAP1 in complex with its DNA target

spinqualitylabelsall models 2ko0 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2ko0 is a 3 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: ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease THAP1_HUMAN Defects in THAP1 are the cause of dystonia type 6 (DYT6) [MIM:602629. DYT6 is a primary torsion dystonia. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. Dystonia type 6 is characterized by onset in early adulthood, cranial or cervical involvement in about half of the cases, and frequent progression to involve multiple body regions.[:] Function THAP1_HUMAN DNA-binding transcription regulator that regulates endothelial cell proliferation and G1/S cell-cycle progression. Specifically binds the 5'-[AT]NTNN[GT]GGCA[AGT]-3' core DNA sequence and acts by modulating expression of pRB-E2F cell-cycle target genes, including RRM1. Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1. May also have pro-apoptopic activity by potentiating both serum-withdrawal and TNF-induced apoptosis. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Human THAP1 is the prototype of a large family of cellular factors sharing an original THAP zinc-finger motif responsible for DNA binding. Human THAP1 regulates endothelial cell proliferation and G1/S cell-cycle progression, through modulation of pRb/E2F cell-cycle target genes including rrm1. Recently, mutations in THAP1 have been found to cause DYT6 primary torsion dystonia, a human neurological disease. We report here the first 3D structure of the complex formed by the DNA-binding domain of THAP1 and its specific DNA target (THABS) found within the rrm1 target gene. The THAP zinc finger uses its double-stranded beta-sheet to fill the DNA major groove and provides a unique combination of contacts from the beta-sheet, the N-terminal tail and surrounding loops toward the five invariant base pairs of the THABS sequence. Our studies reveal unprecedented insights into the specific DNA recognition mechanisms within this large family of proteins controlling cell proliferation, cell cycle and pluripotency. Structural determinants of specific DNA-recognition by the THAP zinc finger.,Campagne S, Saurel O, Gervais V, Milon A Nucleic Acids Res. 2010 Jun;38(10):3466-76. Epub 2010 Feb 9. PMID:20144952 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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