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Analysis of the costructure of the simian virus 40 T-antigen origin binding domain with site I reveals a correlation between GAGGC spacing and spiral assembly.

Meinke G, Phelan PJ, Harrison CJ, Bullock PA
J Virol 87 2923-34 (2013)
Cited: 4 times
EuropePMC logo PMID: 23269808

Abstract

Polyomavirus origins of replication contain multiple occurrences of G(A/G)GGC, the high-affinity binding element for the viral initiator T-antigen (T-ag). The site I regulatory region of simian virus 40, involved in the repression of transcription and the enhancement of DNA replication initiation, contains two GAGGC sequences arranged head to tail and separated by a 7-bp AT-rich sequence. We have solved a 3.2-Å costructure of the SV40 origin-binding domain (OBD) bound to site I. We have also established that T-ag assembly on site I is limited to the formation of a single hexamer. These observations have enabled an analysis of the role(s) of the OBDs bound to the site I pentanucleotides in hexamer formation. Of interest, they reveal a correlation between the OBDs bound to site I and a pair of OBD subunits in the previously described hexameric spiral structure. Based on these findings, we propose that spiral assembly is promoted by pentanucleotide pairs arranged in a head-to-tail manner. Finally, the possibility that spiral assembly by OBD subunits accounts for the heterogeneous distribution of pentanucleotides found in the origins of replication of polyomaviruses is discussed.

Articles - 4fgn mentioned but not cited (3)

  1. The structure of SV40 large T hexameric helicase in complex with AT-rich origin DNA. Gai D, Wang D, Li SX, Chen XS. Elife 5 e18129 (2016)
  2. Insights into the initiation of JC virus DNA replication derived from the crystal structure of the T-antigen origin binding domain. Meinke G, Phelan PJ, Kalekar R, Shin J, Archambault J, Bohm A, Bullock PA. PLoS Pathog 10 e1003966 (2014)
  3. Structural Based Analyses of the JC Virus T-Antigen F258L Mutant Provides Evidence for DNA Dependent Conformational Changes in the C-Termini of Polyomavirus Origin Binding Domains. Meinke G, Phelan PJ, Shin J, Gagnon D, Archambault J, Bohm A, Bullock PA. PLoS Pathog 12 e1005362 (2016)


Articles citing this publication (1)

  1. Crystal structure of an engineered, HIV-specific recombinase for removal of integrated proviral DNA. Meinke G, Karpinski J, Buchholz F, Bohm A. Nucleic Acids Res 45 9726-9740 (2017)


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