2JEX

Transcription activator structure reveals redox control of a replication initiation reaction

Summary for 2JEX

• Entry DOI: 10.2210/pdb2jex/pdb
• Related: 1DBD 1JJH 2BOP 2JEU
• Descriptor: REGULATORY PROTEIN E2 (2 entities in total)
• Functional Keywords: nuclear protein, dna replication, phosphorylation, transcription regulation, viral transcription factor, bovine papillomavirus, replication initiation, early protein, transcription, redox control, e1, e2, oxidation, activator, repressor, dna-binding
• Biological source: BOVINE PAPILLOMAVIRUS TYPE 1
• Total number of polymer chains: 1
• Total formula weight: 23820.59

Authors

Sanders, C.M.,Sizov, D.,Seavers, P.R.,Ortiz-Lombardia, M.,Antson, A.A. (deposition date: 2007-01-24, release date: 2007-05-15, Last modification date: 2023-12-13)

Primary citation

Sanders, C.M.,Sizov, D.,Seavers, P.R.,Ortiz-Lombardia, M.,Antson, A.A.
Transcription Activator Structure Reveals Redox Control of a Replication Initiation Reaction.
Nucleic Acids Res., 35:3504-, 2007

PubMed Abstract: Redox changes are one of the factors that influence cell-cycle progression and that control the processes of cellular proliferation, differentiation, senescence and apoptosis. Proteins regulated through redox-sensitive cysteines have been characterized but specific 'sulphydryl switches' in replication proteins remain to be identified. In bovine papillomavirus type-1, DNA replication begins when the viral transcription factor E2 recruits the viral initiator protein E1 to the origin of DNA replication (ori). Here we show that a novel dimerization interface in the E2 transcription activation domain is stabilized by a disulphide bond. Oxidative cross-linking via Cys57 sequesters the interaction surface between E1 and E2, preventing pre-initiation and replication initiation complex formation. Our data demonstrate that as well as a mechanism for regulating DNA binding, redox reactions can control replication by modulating the tertiary structure of critical protein factors using a specific redox sensor.

PubMed: 17478495
DOI: 10.1093/NAR/GKM166

Experimental method

X-RAY DIFFRACTION (2.35 Å)