title: Atomic snapshots of an RNA packaging motor reveal conformational changes linking ATP hydrolysis to RNA translocation.
abstract: Many viruses package their genome into preformed capsids using packaging motors powered by the hydrolysis of ATP. The hexameric ATPase P4 of dsRNA bacteriophage phi12, located at the vertices of the icosahedral capsid, is such a packaging motor. We have captured crystallographic structures of P4 for all the key points along the catalytic pathway, including apo, substrate analog bound, and product bound. Substrate and product binding have been observed as both binary complexes and ternary complexes with divalent cations. These structures reveal large movements of the putative RNA binding loop, which are coupled with nucleotide binding and hydrolysis, indicating how ATP hydrolysis drives RNA translocation through cooperative conformational changes. Two distinct conformations of bound nucleotide triphosphate suggest how hydrolysis is activated by RNA binding. This provides a model for chemomechanical coupling for a prototype of the large family of hexameric helicases and oligonucleotide translocating enzymes.
authors.affiliation: Division of Structural Biology, The Henry Wellcome Building for Genomic Medicine, Oxford University, Roosevelt Drive, OX3 7BN, United Kingdom.
authors.forename: Erika J
authors.initials: EJ
authors.lastname: Mancini
authors.forename: Denis E
authors.initials: DE
authors.lastname: Kainov
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Grimes
authors.forename: Roman
authors.initials: R
authors.lastname: Tuma
authors.forename: Dennis H
authors.initials: DH
authors.lastname: Bamford
authors.forename: David I
authors.initials: DI
authors.lastname: Stuart
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000595:Amino Acid Sequence / Q000502:physiology; D001665:Binding Sites / Q000502:physiology; D002213:Capsid / Q000378:metabolism; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000821:virology; D006868:Hydrolysis; D046911:Macromolecular Substances; D008958:Models, Molecular; D020409:Molecular Motor Proteins / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D011487:Protein Conformation; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D034443:RNA Transport / Q000502:physiology*; D012330:RNA, Double-Stranded / Q000378:metabolism; D012367:RNA, Viral / Q000737:chemistry / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D046911:Macromolecular Substances; D020409:Molecular Motor Proteins; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D014157:Transcription Factors; D014764:Viral Proteins; C053987:p4 protein, Bacteriophage phi 29; D012313:RNA; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases