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Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
Published on: July 14, 2015
Sequence coevolution between RNA and protein characterized by mutual information between residue triplets.
Relly Brandman1, Yigal Brandman, Vijay S Pande
1Chemical and Systems Biology, Stanford University, Stanford, California, United States of America.
Plos One
|January 27, 2012
Summary
Researchers found the first direct evidence of protein-RNA coevolution in the ribosome. Analyzing residue triplets revealed evolutionary patterns suggesting biophysical constraints drive the coevolution of interacting protein and RNA chains.
Area of Science:
- Molecular Biology
- Evolutionary Biology
- Structural Biology
Background:
- Amino acid coevolution within proteins and nucleic acid coevolution within RNA are well-documented.
- Direct evidence for coevolution between protein and RNA has been lacking.
- The ribosome, a complex of protein and RNA, serves as a model system for studying RNA/protein interactions.
Purpose of the Study:
- To provide the first direct evidence of RNA/protein coevolution.
- To investigate coevolutionary patterns between ribosomal protein L22 and 23S ribosomal RNA.
Main Methods:
- Analysis of mutual information in residue triplets (one RNA, two protein positions) from multiple sequence alignments.
- Comparison of mutual information with residue proximity in 3D structures.
- Examination of structural differences in crystal structures of distinct ribosome species.
Main Results:
- High mutual information in residue triplets correlates with proximity in 3D space, exceeding that of residue doublets.
- Coevolutionary patterns observed in triplets resemble those found in protein-protein coevolution.
- Changes in RNA nucleotides (e.g., pyrimidine to purine) correspond to altered proximal amino acid distributions, supported by structural data showing differential hydrogen bonding.
Conclusions:
- The study presents the first direct evidence of RNA/protein coevolution using higher-order mutual information analysis.
- Biophysical constraints on interacting RNA and protein chains are identified as a significant driving force in their joint evolution.
- The findings highlight the importance of considering coupled evolutionary dynamics in macromolecular complexes like the ribosome.
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