title: Structural and evolutionary classification of G/U wobble basepairs in the ribosome.
abstract: We present a comprehensive structural, evolutionary and molecular dynamics (MD) study of the G/U wobble basepairs in the ribosome based on high-resolution crystal structures, including the recent Escherichia coli structure. These basepairs are classified according to their tertiary interactions, and sequence conservation at their positions is determined. G/U basepairs participating in tertiary interactions are more conserved than those lacking any interactions. Specific interactions occurring in the G/U shallow groove pocket--like packing interactions (P-interactions) and some phosphate backbone interactions (phosphate-in-pocket interactions)--lead to higher G/U conservation than others. Two salient cases of unique phylogenetic compensation are discovered. First, a P-interaction is conserved through a series of compensatory mutations involving all four participating nucleotides to preserve or restore the G/U in the optimal orientation. Second, a G/U basepair forming a P-interaction and another one forming a phosphate-in-pocket interaction are replaced by GNRA loops that maintain similar tertiary contacts. MD simulations were carried out on eight P-interactions. The specific GU/CG signature of this interaction observed in structure and sequence analysis was rationalized, and can now be used for improving sequence alignments.
authors.affiliation: Department of Chemistry and Center for Biomolecular Sciences, Bowling Green State University, OH 43403, USA. Mali@bgnet.bgsu.edu
authors.forename: Ali
authors.initials: A
authors.lastname: Mokdad
authors.forename: Maryna V
authors.initials: MV
authors.lastname: Krasovska
authors.forename: Jiri
authors.initials: J
authors.lastname: Sponer
authors.forename: Neocles B
authors.initials: NB
authors.lastname: Leontis
mesh_terms: D020029:Base Pairing; D001483:Base Sequence; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D006147:Guanine / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010710:Phosphates / Q000737:chemistry; D019642:RNA, Archaeal / Q000737:chemistry; D012329:RNA, Bacterial / Q000737:chemistry; D012335:RNA, Ribosomal / Q000737:chemistry*; D012336:RNA, Ribosomal, 16S / Q000737:chemistry; D012338:RNA, Ribosomal, 23S / Q000737:chemistry; D012341:RNA, Ribosomal, 5S / Q000737:chemistry; D012270:Ribosomes / Q000737:chemistry; D017423:Sequence Analysis, RNA; D014498:Uracil / Q000737:chemistry*
chemical_list: D010710:Phosphates; D019642:RNA, Archaeal; D012329:RNA, Bacterial; D012335:RNA, Ribosomal; D012336:RNA, Ribosomal, 16S; D012338:RNA, Ribosomal, 23S; D012341:RNA, Ribosomal, 5S; D014498:Uracil; D006147:Guanine