Amino acid composition of protein termini are biased in different manners.

An exhaustive statistical analysis of the amino acid sequences at the carboxyl (C) and amino (N) termini of proteins and of coding nucleic acid sequences at the 5' side of the stop codons was undertaken. At the N ends, Met and Ala residues are over-represented at the first (+1) position whereas at positions 2 and 5 Thr is preferred. These peculiarities at N-termini are most probably related to the mechanism of initiation of translation (for Met) and to the mechanisms governing the life-span of proteins via regulation of their degradation (for Ala and Thr). We assume that the C-terminal bias facilitates fixation of the C ends on the protein globule by a preference for charged and Cys residues. The terminal biases, a novel feature of protein structure, have to be taken into account when molecular evolution, three-dimensional structure, initiation and termination of translation, protein folding and life-span are concerned. In addition, the bias of protein termini composition is an important feature which should be considered in protein engineering experiments.

[1]  L. Kisselev,et al.  Eukaryotic release factor 1 (eRF1) abolishes readthrough and competes with suppressor tRNAs at all three termination codons in messenger RNA. , 1997, Nucleic acids research.

[2]  D J Prockop,et al.  Collagens: molecular biology, diseases, and potentials for therapy. , 1995, Annual review of biochemistry.

[3]  B. Tidor,et al.  Do salt bridges stabilize proteins? A continuum electrostatic analysis , 1994, Protein science : a publication of the Protein Society.

[4]  S. Korolev,et al.  Termination of translation in bacteria may be modulated via specific interaction between peptide chain release factor 2 and the last peptidyl-tRNA(Ser/Phe). , 1993, Nucleic acids research.

[5]  F Sherman,et al.  Methionine or not methionine at the beginning of a protein , 1985, BioEssays : news and reviews in molecular, cellular and developmental biology.

[6]  T. Baldwin,et al.  Implications of N and C-terminal proximity for protein folding. , 1996, Journal of molecular biology.

[7]  Mark E. Dalphin,et al.  The translational termination signal database , 1993, Nucleic Acids Res..

[8]  E. Trifonov.  Translation framing code and frame-monitoring mechanism as suggested by the analysis of mRNA and 16 S rRNA nucleotide sequences. , 1987, Journal of molecular biology.

[9]  O. W. Odom,et al.  Cotranslational folding of nascent proteins on Escherichia coli ribosomes. , 1995, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[10]  S. Arfin,et al.  The sequence of porcine protein NH2-terminal asparagine amidohydrolase. A new component of the N-end Rule pathway. , 1995, The Journal of biological chemistry.

[11]  A. Varshavsky,et al.  The N-end rule: functions, mysteries, uses. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[12]  R. Buckingham,et al.  Polypeptide chain release factors , 1997, Molecular microbiology.

[13]  S. Arfin,et al.  A Mouse Amidase Specific for N-terminal Asparagine , 1996, The Journal of Biological Chemistry.

[14]  A. Varshavsky,et al.  In vivo half-life of a protein is a function of its amino-terminal residue. , 1986, Science.

[15]  K. Dill.  Dominant forces in protein folding. , 1990, Biochemistry.

[16]  L. Isaksson,et al.  Emerging Understanding of Translation Termination , 1996, Cell.

[17]  A. Fersht,et al.  Strength and co-operativity of contributions of surface salt bridges to protein stability. , 1990, Journal of molecular biology.

[18]  B. Friguet,et al.  Folding on the ribosome of Escherichia coli tryptophan synthase beta subunit nascent chains probed with a conformation-dependent monoclonal antibody. , 1992, Journal of molecular biology.

[19]  J. Thornton,et al.  Ion-pairs in proteins. , 1983, Journal of molecular biology.

[20]  A. Fersht,et al.  Surface electrostatic interactions contribute little of stability of barnase. , 1991, Journal of molecular biology.

[21]  Chris M. Brown,et al.  The signal for the termination of protein synthesis in procaryotes. , 1990, Nucleic acids research.

[22]  M. Summers,et al.  NMR structure of HMfB from the hyperthermophile, Methanothermus fervidus, confirms that this archaeal protein is a histone. , 1996, Journal of molecular biology.

[23]  W P Tate,et al.  Three, four or more: the translational stop signal at length , 1996, Molecular microbiology.

[24]  J M Thornton,et al.  Amino and carboxy-terminal regions in globular proteins. , 1983, Journal of molecular biology.

[25]  E. V. Makeyev,et al.  Cotranslational folding of proteins. , 1995, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[26]  A. Fersht,et al.  Estimating the contribution of engineered surface electrostatic interactions to protein stability by using double-mutant cycles. , 1990, Biochemistry.

[27]  R. Goldman,et al.  Influence of codon context on UGA suppression and readthrough. , 1992, Journal of Molecular Biology.

[28]  V. Tumanyan,et al.  COOH‐terminal decamers in proteins are non‐random , 1997, FEBS letters.

[29]  Chris M. Brown,et al.  Sequence analysis suggests that tetra-nucleotides signal the termination of protein synthesis in eukaryotes. , 1990, Nucleic acids research.

[30]  A. Varshavsky.  The N-end rule , 1992, Cell.

[31]  A. Fedorov,et al.  Contribution of cotranslational folding to the rate of formation of native protein structure. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[32]  R. Buckingham,et al.  Third position base changes in codons 5' and 3' adjacent UGA codons affect UGA suppression in vivo. , 1990, Biochimica et biophysica acta.