2LUS

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

Summary for 2LUS

• Entry DOI: 10.2210/pdb2lus/pdb
• NMR Information: BMRB: 18539
• Descriptor: Thioredoxion (1 entity in total)
• Functional Keywords: cr-trp16, oxidoreductase
• Biological source: Carcinoscorpius rotundicauda (mangrove horseshoe crab)
• Total number of polymer chains: 1
• Total formula weight: 16062.34

Authors

Giri, P.K.,Fan, J.,Kunchithapadam, S.,Sivaraman, J. (deposition date: 2012-06-21, release date: 2012-07-11, Last modification date: 2024-05-01)

Primary citation

Giri, P.K.,Jing-Song, F.,Shanmugam, M.K.,Ding, J.L.,Sethi, G.,Swaminathan, K.,Sivaraman, J.
NMR structure of Carcinoscorpius rotundicauda thioredoxin-related protein 16 and its role in regulating transcription factor NF-kB activity.
J.Biol.Chem., 287:29417-29428, 2012

PubMed Abstract: 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-κB, 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-κB 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-κB and showed that Cr-TRP16 exists as a dimer under physiological conditions, and only the dimeric form binds to NF-κB and enhances its DNA binding activity by directly reducing the cysteines in the DNA-binding motif of NF-κB. The C15S mutant of Cr-TRP16 was unable to dimerize and hence does not bind to NF-κB. Based on our finding and combined with the literature, we propose a model of how Cr-TRP16 is likely to bind to NF-κB. These findings elucidate the molecular mechanism by which NF-κB activation is regulated through Cr-TRP16.

PubMed: 22763700
DOI: 10.1074/jbc.M112.379859

Experimental method

SOLUTION NMR