Phage P4 origin-binding domain structure reveals a mechanism for regulation of DNA-binding activity by homo- and heterodimerization of winged helix proteins

Molecular Microbiology
Hye-Jeong YeoGabriel Waksman

Abstract

The origin-binding domain of the gpalpha protein of phage P4 (P4-OBD) mediates origin recognition and regulation of gpalpha activity by the protein Cnr. We have determined the crystal structure of P4-OBD at 2.95 A resolution. The structure of P4-OBD is that of a dimer with pseudo twofold symmetry. Each subunit has a winged helix topology with a unique structure among initiator proteins. The only structural homologue of the P4-OBD subunit is the DNA-binding domain of the eukaryotic transcriptional activator Rfx1. Based on this structural alignment, a model for origin recognition by the P4-OBD dimer is suggested. P4-OBD mutations that interfere with Cnr binding locate to the dimer interface, indicating that Cnr acts by disrupting the gpalpha dimer. P4-OBD dimerization is mediated by helices alpha1 and alpha3 in both subunits, a mode of winged helix protein dimerization that is reminiscent of that of the eukaryotic transcription factors E2F and DP. This, in turn, suggests that Cnr is also a winged helix protein, a possibility that is supported by previously unreported sequence homologies between Cnr and Rfx1 and homology modelling. Hence, in a mechanism that appears to be conserved from phage to man, the DNA-binding activity of wi...Continue Reading

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Citations

Apr 6, 2005·FEMS Microbiology Reviews·L AravindLakshminarayan M Iyer
Oct 7, 2008·Journal of Molecular Biology·Takeshi YokoyamaHye-Jeong Yeo
Apr 27, 2016·Nucleic Acids Research·Darius KazlauskasČeslovas Venclovas

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