Subunit rearrangement accompanies sequence-specific DNA binding by the bovine papillomavirus-1 E2 protein.
The 2.5 A crystal structures of the DNA-binding domain of the E2 protein from bovine papillomavirus strain 1 and its complex with DNA are presented. E2 is a transcriptional regulatory protein that is also involved in viral DNA replication. It is the structural prototype for a novel class of DNA-binding proteins: dimeric beta-barrels with surface alpha-helices that serve as recognition helices. These helices contain the amino-acid residues involved in sequence-specifying interactions. The E2 proteins from different papillomavirus strains recognize and bind to the same consensus 12 base-pair DNA sequence. However, recent evidence from solution studies points to differences in the mechanisms by which E2 from the related viral strains bovine papillomavirus-1 and human papillomavirus-16 discriminate between DNA targets based on non-contacted nucleotide sequences. This report provides evidence that sequence-specific DNA-binding is accompanied by a rearrangement of protein subunits and deformation of the DNA. These results suggest that, along with DNA sequence-dependent conformational properties, protein subunit orientation plays a significant role in the mechanisms of target selection utilized by E2.
Hegde
R S
RS
Department of Biochemistry and Program in Structural Biology, Skirball Institute of Biomolecular Medicine, New York University Medical Center, 540 First Avenue, New York, NY 10016, USA.
Wang
A F
AF
Kim
S S
SS
Schapira
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D052688:Bovine papillomavirus 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002417:Cattle; D018360:Crystallography, X-Ray; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D006801:Humans; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D004279:DNA, Viral; D004268:DNA-Binding Proteins; C051550:E2 protein, Bovine papillomavirus; C054855:E2 protein, Human papillomavirus type 16; D046911:Macromolecular Substances; D009856:Oncogene Proteins, Viral; D014764:Viral Proteins