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CRYSTAL STRUCTURE OF E. COLI SEQA COMPLEXED WITH HEMIMETHYLATED DNACRYSTAL STRUCTURE OF E. COLI SEQA COMPLEXED WITH HEMIMETHYLATED DNA
Structural highlights
Function[SEQA_ECOLI] Negative regulator of replication initiation, which contributes to regulation of DNA replication and ensures that replication initiation occurs exactly once per chromosome per cell cycle. Binds to pairs of hemimethylated GATC sequences in the oriC region, thus preventing assembly of replication proteins and re-initiation at newly replicated origins. Repression is relieved when the region becomes fully methylated. Can also bind to hemimethylated GATC sequences outside of oriC region. Binds, with less affinity, to fully methylated GATC sites and affects timing of replication. May play a role in chromosome organization and gene regulation.[1] [2] [3] [4] [5] [6] 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 PubMedThe SeqA protein binds clusters of fully methylated or hemimethylated GATC sequences at oriC and negatively modulates the initiation of DNA replication. We find that SeqA can be proteolytically cleaved into an N-terminal multimerization and a C-terminal DNA-binding domain and have determined the crystal structure of the C-terminal domain in complex with a hemimethylated GATC site. SeqA makes direct hydrogen bonds and van der Waals contacts with the hemimethylated A-T base pair in addition to interactions with the surrounding bases and DNA backbone. The tetrameric protein-DNA complex found in the crystal suggests that SeqA binds multiple GATC sites on separate DNA duplexes, altering the overall DNA topology and sequestering oriC from replication initiation. Insights into negative modulation of E. coli replication initiation from the structure of SeqA-hemimethylated DNA complex.,Guarne A, Zhao Q, Ghirlando R, Yang W Nat Struct Biol. 2002 Nov;9(11):839-43. PMID:12379844[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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