title: The crystal structure of the Rev binding element of HIV-1 reveals novel base pairing and conformational variability.
abstract: The crystal and molecular structure of an RNA duplex corresponding to the high affinity Rev protein binding element (RBE) has been determined at 2.1-A resolution. Four unique duplexes are present in the crystal, comprising two structural variants. In each duplex, the RNA double helix consists of an annealed 12-mer and 14-mer that form an asymmetric internal loop consisting of G-G and G-A noncanonical base pairs and a flipped-out uridine. The 12-mer strand has an A-form conformation, whereas the 14-mer strand is distorted to accommodate the bulges and noncanonical base pairing. In contrast to the NMR model of the unbound RBE, an asymmetric G-G pair with N2-N7 and N1-O6 hydrogen bonding, is formed in each helix. The G-A base pairing agrees with the NMR structure in one structural variant, but forms a novel water-mediated pair in the other. A backbone flip and reorientation of the G-G base pair is required to assume the RBE conformation present in the NMR model of the complex between the RBE and the Rev peptide.
authors.affiliation: Macromolecular Crystallography Facility and Structural Biology Department, Melvin Calvin Building, Physical Biosciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, CA 94720, USA.
authors.forename: L W
authors.initials: LW
authors.lastname: Hung
authors.forename: E L
authors.initials: EL
authors.lastname: Holbrook
authors.forename: S R
authors.initials: SR
authors.lastname: Holbrook
mesh_terms: D001483:Base Sequence; D018360:Crystallography, X-Ray; D015694:Gene Products, rev / Q000737:chemistry* / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism; D009690:Nucleic Acid Conformation; D009843:Oligoribonucleotides / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012367:RNA, Viral / Q000737:chemistry* / Q000378:metabolism; D054321:rev Gene Products, Human Immunodeficiency Virus
chemical_list: D015694:Gene Products, rev; D009687:Nuclear Proteins; D009843:Oligoribonucleotides; D012367:RNA, Viral; C069802:nuclear factor, RRE binding; D054321:rev Gene Products, Human Immunodeficiency Virus