期刊
NUCLEIC ACIDS RESEARCH
卷 34, 期 5, 页码 1326-1341出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkl025
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资金
- NIGMS NIH HHS [R15 GM055898-04, 2 R15 GM055898-03, R15 GM055898] Funding Source: Medline
- Wellcome Trust [GR067507] Funding Source: Medline
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R15GM055898] Funding Source: NIH RePORTER
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.
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