2lus | pdb_00002lus

NMR structure of Carcinoscorpius rotundicauda thioredoxin related protein 16 and its role in regulating transcription factor NF-kB activity

spinqualitylabelsall models 2lus, 20 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2lus is a 1 chain structure with sequence from Carcinoscorpius rotundicauda. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Thioredoxins (Trxs), which play a key role in maintaining a redox environment in the cell, are found in almost all organisms. Trxs act as potential reducing agents of disulfide bonds and contain two vicinal cysteines in a CXXC motif at the active site. Trx is also known to activate the DNA binding activity of NF-kappaB, an important transcription factor. Previously, Trx-related protein 16 from Carcinoscorpius rotundicauda (Cr-TRP16), a 16-kDa Trx-like protein that contains a WCPPC motif, was reported. Here we present the NMR structure of the reduced form of Cr-TRP16, along with its regulation of NF-kappaB activity. Unlike other 16-kDa Trx-like proteins, Cr-TRP16 contains an additional Cys residue (Cys-15, at the N terminus), through which it forms a homodimer. Moreover, we have explored the molecular basis of Cr-TRP16-mediated activation of NF-kappaB and showed that Cr-TRP16 exists as a dimer under physiological conditions, and only the dimeric form binds to NF-kappaB and enhances its DNA binding activity by directly reducing the cysteines in the DNA-binding motif of NF-kappaB. The C15S mutant of Cr-TRP16 was unable to dimerize and hence does not bind to NF-kappaB. Based on our finding and combined with the literature, we propose a model of how Cr-TRP16 is likely to bind to NF-kappaB. These findings elucidate the molecular mechanism by which NF-kappaB activation is regulated through Cr-TRP16. NMR structure of Carcinoscorpius rotundicauda thioredoxin-related protein 16 and its role in regulating transcription factor NF-kappaB activity.,Giri PK, Jing-Song F, Shanmugam MK, Ding JL, Sethi G, Swaminathan K, Sivaraman J J Biol Chem. 2012 Aug 24;287(35):29417-28. doi: 10.1074/jbc.M112.379859. Epub, 2012 Jul 3. PMID:22763700 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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