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PDBsum entry 2jex
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Transcription
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PDB id
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2jex
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References listed in PDB file
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Key reference
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Title
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Transcription activator structure reveals redox control of a replication initiation reaction.
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Authors
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C.M.Sanders,
D.Sizov,
P.R.Seavers,
M.Ortiz-Lombardía,
A.A.Antson.
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Ref.
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Nucleic Acids Res, 2007,
35,
3504-3515.
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PubMed id
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Abstract
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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.
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