title: X-ray structure of RLI, an essential twin cassette ABC ATPase involved in ribosome biogenesis and HIV capsid assembly.
abstract: The ABC ATPase RNase-L inhibitor (RLI) emerges as a key enzyme in ribosome biogenesis, formation of translation preinitiation complexes, and assembly of HIV capsids. To help reveal the structural mechanism of RLI, we determined the Mg2+-ADP bound crystal structure of the twin cassette ATPase of P. furiosus RLI at 1.9 A resolution and analyzed functional motifs in yeast in vivo. RLI shows similarities but also differences to known ABC enzyme structures. Twin nucleotide binding domains (NBD1 and NBD2) are arranged to form two composite active sites in their interface cleft, indicating they undergo the ATP-driven clamp-like motion of the NBDs of ABC transporters. An unusual "hinge" domain along the NBD1:NBD2 interface provides a frame for association and possibly ATP-driven conformational changes of the NBDs. Our results establish a first structural basis for ABC domain heterodimers and suggest that RLI may act as mechanochemical enzyme in ribosome and HIV capsid biogenesis.
authors.affiliation: Gene Center, Department of Chemistry and Biochemistry, University of Munich, Feodor-Lynen-Strasse 25, D-81377 Munich, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Karcher
authors.forename: Katharina
authors.initials: K
authors.lastname: Büttner
authors.forename: Birgit
authors.initials: B
authors.lastname: Märtens
authors.forename: Ralf-Peter
authors.initials: RP
authors.lastname: Jansen
authors.forename: Karl-Peter
authors.initials: KP
authors.lastname: Hopfner
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000378:metabolism*; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D002213:Capsid / Q000378:metabolism*; D018360:Crystallography, X-Ray; D017931:DNA Primers; D006678:HIV / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011487:Protein Conformation; D012270:Ribosomes; D017386:Sequence Homology, Amino Acid
chemical_list: D017931:DNA Primers; D000251:Adenosine Triphosphatases