Insights into specific DNA recognition during the assembly of a viral genome packaging machine.
Terminase enzymes mediate genome "packaging" during the reproduction of DNA viruses. In lambda, the gpNu1 subunit guides site-specific assembly of terminase onto DNA. The structure of the dimeric DNA binding domain of gpNu1 was solved using nuclear magnetic resonance spectroscopy. Its fold contains a unique winged helix-turn-helix (wHTH) motif within a novel scaffold. Surprisingly, a predicted P loop ATP binding motif is in fact the wing of the DNA binding motif. Structural and genetic analysis has identified determinants of DNA recognition specificity within the wHTH motif and the DNA recognition sequence. The structure reveals an unexpected DNA binding mode and provides a mechanistic basis for the concerted action of gpNu1 and Escherichia coli integration host factor during assembly of the packaging machinery.
de Beer
Tonny
T
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262, USA. tonny.debeer@astrazeneca.com
Fang
Jenny
J
Ortega
Marcos
M
Yang
Qin
Q
Maes
Levi
L
Duffy
Carol
C
Berton
Nancy
N
Sippy
Jean
J
Overduin
Michael
M
Feiss
Michael
M
Catalano
Carlos Enrique
CE
D000255:Adenosine Triphosphate / Q000378:metabolism; D010582:Bacteriophage lambda / Q000235:genetics; D001665:Binding Sites; D004279:DNA, Viral / Q000378:metabolism*; D019281:Dimerization; D004926:Escherichia coli; D016679:Genome, Viral; D019077:Helix-Turn-Helix Motifs; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D017510:Protein Folding; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000378:metabolism*; D019065:Virus Assembly / Q000235:genetics*
D004279:DNA, Viral; D014764:Viral Proteins; C050856:lambda phage protein Nu 1; D000255:Adenosine Triphosphate