title: Adenine recognition is a key checkpoint in the energy release mechanism of phage T4 DNA packaging motor.
abstract: ATP is the source of energy for numerous biochemical reactions in all organisms. Tailed bacteriophages use ATP to drive powerful packaging machines that translocate viral DNA into a procapsid and compact it to near-crystalline density. Here we report that a complex network of interactions dictates adenine recognition and ATP hydrolysis in the pentameric phage T4 large "terminase" (gp17) motor. The network includes residues that form hydrogen bonds at the edges of the adenine ring (Q138 and Q143), base-stacking interactions at the plane of the ring (I127 and R140), and cross-talking bonds between adenine, triphosphate, and Walker A P-loop (Y142, Q143, and R140). These interactions are conserved in other translocases such as type I/type III restriction enzymes and SF1/SF2 helicases. Perturbation of any of these interactions, even the loss of a single hydrogen bond, leads to multiple defects in motor functions. Adenine recognition is therefore a key checkpoint that ensures efficient ATP firing only when the fuel molecule is precisely engaged with the motor. This may be a common feature in the energy release mechanism of ATP-driven molecular machines that carry out numerous biomolecular reactions in biological systems.
authors.affiliation: Department of Biology, The Catholic University of America, 620 Michigan Avenue NE, Washington, DC 20064, USA.
authors.forename: Kiran
authors.initials: K
authors.lastname: Kondabagil
authors.forename: Bonnie
authors.initials: B
authors.lastname: Draper
authors.forename: Venigalla B
authors.initials: VB
authors.lastname: Rao
mesh_terms: D000225:Adenine / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D017122:Bacteriophage T4 / Q000502:physiology*; D004252:DNA Mutational Analysis; D042003:DNA Packaging; D004279:DNA, Viral / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019065:Virus Assembly
chemical_list: D004279:DNA, Viral; D050505:Mutant Proteins; D014764:Viral Proteins; C065038:gp17 protein, Enterobacteria phage T4; D000255:Adenosine Triphosphate; D000225:Adenine