Characterization of oligopeptide patterns in large protein sets

Bresell, Anders; Persson, Bengt

doi:10.1186/1471-2164-8-346

Cited by 12 publications

(10 citation statements)

References 32 publications

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“…Fortunately, our findings regarding SCS usage have been confirmed independently by other groups [ 28 , 29 ]. We now know that there are rare or non-existent SCSs in the nr-aa database (i.e., the universal proteome), and they can be synthesized chemically and biologically with little difficulty [ 14 ].…”

Section: Simple Frequency-based Approachsupporting

confidence: 87%

A Frequency-Based Linguistic Approach to Protein Decoding and Design: Simple Concepts, Diverse Applications, and the SCS Package

Motomura

Nakamura

Otaki

2013

Computational and Structural Biotechnology Journal

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Protein structure and function information is coded in amino acid sequences. However, the relationship between primary sequences and three-dimensional structures and functions remains enigmatic. Our approach to this fundamental biochemistry problem is based on the frequencies of short constituent sequences (SCSs) or words. A protein amino acid sequence is considered analogous to an English sentence, where SCSs are equivalent to words. Availability scores, which are defined as real SCS frequencies in the non-redundant amino acid database relative to their probabilistically expected frequencies, demonstrate the biological usage bias of SCSs. As a result, this frequency-based linguistic approach is expected to have diverse applications, such as secondary structure specifications by structure-specific SCSs and immunological adjuvants with rare or non-existent SCSs. Linguistic similarities (e.g., wide ranges of scale-free distributions) and dissimilarities (e.g., behaviors of low-rank samples) between proteins and the natural English language have been revealed in the rank-frequency relationships of SCSs or words. We have developed a web server, the SCS Package, which contains five applications for analyzing protein sequences based on the linguistic concept. These tools have the potential to assist researchers in deciphering structurally and functionally important protein sites, species-specific sequences, and functional relationships between SCSs. The SCS Package also provides researchers with a tool to construct amino acid sequences de novo based on the idiomatic usage of SCSs.

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Section: Simple Frequency-based Approachsupporting

confidence: 87%

A Frequency-Based Linguistic Approach to Protein Decoding and Design: Simple Concepts, Diverse Applications, and the SCS Package

Motomura

Nakamura

Otaki

2013

Computational and Structural Biotechnology Journal

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“…This makes it possible to perform largescale investigations of sequence patterns (cf. [ 102 ]) and provides increased information about protein family members and their evolution. Early in 2007, close to 400 complete genomes were available in the databases [ 103 – 105 ].…”

Section: Mdrs In Complete Genomesmentioning

confidence: 99%

Medium- and short-chain dehydrogenase/reductase gene and protein families

Persson

Hedlund

Jörnvall

2008

Cell. Mol. Life Sci.

157

112

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Abstract. The MDR superfamily with~350-residue subunits contains the classical liver alcohol dehydrogenase (ADH), quinone reductase, leukotriene B4 dehydrogenase and many more forms. ADH is a dimeric zinc metalloprotein and occurs as five different classes in humans, resulting from gene duplications during vertebrate evolution, the first one traced to~500 MYA (million years ago) from an ancestral formaldehyde dehydrogenase line. Like many duplications at that time, it correlates with enzymogenesis of new activities, contributing to conditions for emergence of vertebrate land life from osseous fish. The speed of changes correlates with function, as do differential evolutionary patterns in separate segments. Subsequent recognitions now define at least 40 human MDR members in the Uniprot database (correA C H T U N G T R E N N U N G sponding to 25 genes when excluding close homologues), and in all species at least 10 888 entries. Overall, variability is large, but like for many dehydrogenases, subdivided into constant and variable forms, corresponding to household and emerging enzyme activities, respectively. This review covers basic facts and describes eight large MDR families and nine smaller families. Combined, they have specific substrates in metabolic pathways, some with wide substrate specificity, and several with little known functions.

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“…Interestingly, contrary to statistical predictions, certain 5 aa and 6 aa peptide combinations are absent from all publicly available proteome sequences [8] , [9] . Short 5–6 aa sequences have been shown to be important in the functional activity of enzymes, cell growth and hormone regulation, transcript expression, proteases, epitope binding, and immune activation [3] , [8] , [10] , [11] . This suggests that short peptide sequences that are not found in humans, other mammals, or other organisms could have biological function; if incorporated, for example into existing vaccines or other therapies.…”

Section: Introductionmentioning

confidence: 99%

Pentamers Not Found in the Universal Proteome Can Enhance Antigen Specific Immune Responses and Adjuvant Vaccines

et al. 2012

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Certain short peptides do not occur in humans and are rare or non-existent in the universal proteome. Antigens that contain rare amino acid sequences are in general highly immunogenic and may activate different arms of the immune system. We first generated a list of rare, semi-common, and common 5-mer peptides using bioinformatics tools to analyze the UniProtKB database. Experimental observations indicated that rare and semi-common 5-mers generated stronger cellular responses in comparison with common-occurring sequences. We hypothesized that the biological process responsible for this enhanced immunogenicity could be used to positively modulate immune responses with potential application for vaccine development. Initially, twelve rare 5-mers, 9-mers, and 13-mers were incorporated in frame at the end of an H5N1 hemagglutinin (HA) antigen and expressed from a DNA vaccine. The presence of some 5-mer peptides induced improved immune responses. Adding one 5-mer peptide exogenously also offered improved clinical outcome and/or survival against a lethal H5N1 or H1N1 influenza virus challenge in BALB/c mice and ferrets, respectively. Interestingly, enhanced anti-HBsAg antibody production by up to 25-fold in combination with a commercial Hepatitis B vaccine (Engerix-B, GSK) was also observed in BALB/c mice. Mechanistically, NK cell activation and dependency was observed with enhancing peptides ex vivo and in NK-depleted mice. Overall, the data suggest that rare or non-existent oligopeptides can be developed as immunomodulators and supports the further evaluation of some 5-mer peptides as potential vaccine adjuvants.

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Characterization of oligopeptide patterns in large protein sets

Cited by 12 publications

References 32 publications

A Frequency-Based Linguistic Approach to Protein Decoding and Design: Simple Concepts, Diverse Applications, and the SCS Package

A Frequency-Based Linguistic Approach to Protein Decoding and Design: Simple Concepts, Diverse Applications, and the SCS Package

Medium- and short-chain dehydrogenase/reductase gene and protein families

Pentamers Not Found in the Universal Proteome Can Enhance Antigen Specific Immune Responses and Adjuvant Vaccines

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