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Availability of short amino acid sequences in proteins

¹ Department of Biological Sciences and
² Department of Information Science, Kanagawa University, Hiratsuka, Kanagawa 259-1293, Japan

(RECEIVED August 31, 2004; FINAL REVISION November 9, 2004; ACCEPTED November 10, 2004)

Much attention is being paid to protein databases as an important information source for proteome research. Although used extensively for similarity searches, protein databases themselves have not fully been characterized. In a systematic attempt to reveal protein-database characters that could contribute to revealing how protein chains are constructed, frequency distributions of all possible combinatorial sets of three, four, and five amino acids ("triplets," "quartets," and "pentats"; collectively called constituent sequences) have been examined in the nonredundant (nr) protein database, demonstrating the existence of nonrandom bias in their "availability" at the population level. Nonexistent short sequences of pentats were found that showed low availability in biological proteins against their expected probabilities of occurrence. Among them, six representative ones were successfully synthesized as peptides with reasonably high yields in a conventional Fmoc method, excluding the possibility that a putative physicochemical energy barrier in forming them could be a direct cause for the low availability. They were also expressed as soluble fusion proteins in a conventional Escherichia coli BL21Star(DE3) system with reasonably high yield, again excluding a possible difficulty in their biological synthesis. Together, these results suggest that information on three-dimensional structures and functions of proteins exists in the context of connections of short constituent sequences, and that proteins are composed of evolutionarily selected constituent sequences, which are reflected in their availability differences in the database. These results may have biological implications for protein structural studies.

Keywords: protein sequence; database search; sequence availability; constituent sequence; rare short sequence

Article published online ahead of print. Article and publication date are at http://www.proteinscience.org/cgi/doi/10.1110/ps.041092605.

Reprint requests to: Joji M. Otaki, Department of Biological Sciences, Kanagawa University, 2946 Tsuchiya, Hiratsuka, Kanagawa 259-1293, Japan; e-mail: otaki{at}bio.kanagawa-u.ac.jp ; fax: 81-463-58-9684.

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