Abstract
Abstract
Background
All the information necessary for protein folding is supposed to be present in the amino acid sequence. It is still not possible to provide specific ab initio structure predictions by bioinformatical methods. It is suspected that additional folding information is present in protein coding nucleic acid sequences, but this is not represented by the known genetic code.
Results
Nucleic acid subsequences comprising the 1st and/or 3rd codon residues in mRNAs express significantly higher free folding energy (FFE) than the subsequence containing only the 2nd residues (p < 0.0001, n = 81). This periodic FFE difference is not present in introns. It is therefore a specific physico-chemical characteristic of coding sequences and might contribute to unambiguous definition of codon boundaries during translation. The FFEs of the 1st and 3rd residues are additive, which suggests that these residues contain a significant number of complementary bases and that may contribute to selection for local RNA secondary structures in coding regions. This periodic, codon-related structure-formation of mRNAs indicates a connection between the structures of exons and the corresponding (translated) proteins. The folding energy dot plots of RNAs and the residue contact maps of the coded proteins are indeed similar. Residue contact statistics using 81 different protein structures confirmed that amino acids that are coded by partially reverse and complementary codons (Watson-Crick (WC) base pairs at the 1st and 3rd codon positions and translated in reverse orientation) are preferentially co-located in protein structures.
Conclusion
Exons are distinguished from introns, and codon boundaries are physico-chemically defined, by periodically distributed FFE differences between codon positions. There is a selection for local RNA secondary structures in coding regions and this nucleic acid structure resembles the folding profiles of the coded proteins. The preferentially (specifically) interacting amino acids are coded by partially complementary codons, which strongly supports the connection between mRNA and the corresponding protein structures and indicates that there is protein folding information in nucleic acids that is not present in the genetic code. This might suggest an additional explanation of codon redundancy.
Publisher
Springer Science and Business Media LLC
Subject
Health Informatics,Modelling and Simulation
Reference37 articles.
1. Anfinsen CB, Redfield RR, Choate WI, Page J, Carroll WR: Studies on the gross structure, cross-linkages, and terminal sequences in ribonuclease. J Biol Chem. 1954, 207: 201-210.
2. Levinthal C: How to fold graciously in Mossbauer spectroscopy in biological systems. Proceedings of a Meeting held at Allerton House, Monticello, IL. Edited by: Debrunner P, Tsibris JCM, Munck E. 1969, Urbana, IL: University of Illinois Press, 22-24.
3. Klepeis JL, Floudas AC: ASTRA-FOLD: a combinatorial and global optimization framework for ab initio prediction of three-dimensional structures of proteins from the amino acid sequence. Biochem J. 2003, 85: 2119-2146.
4. Walter S, Buchner J: Molecular chaperones – cellular machines for protein folding. Angew Chem Int Ed Engl. 2002, 41: 1098-1113. 10.1002/1521-3773(20020402)41:7<1098::AID-ANIE1098>3.0.CO;2-9.
5. Komar AA, Kommer A, Krasheninnikov IA, Spirin AS: Cotranslational folding of globin. J Biol Chem. 1997, 272: 10646-10651. 10.1074/jbc.272.16.10646.
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