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. 2014 Jan;14(1):42-50.
doi: 10.1002/pmic.201300416. Epub 2013 Dec 11.

Sequence-derived structural features driving proteolytic processing

Alexander A Belushkin  1 , Dmitry V Vinogradov, Mikhail S Gelfand, Andrei L Osterman, Piotr Cieplak, Marat D Kazanov
Affiliations

Sequence-derived structural features driving proteolytic processing

Alexander A Belushkin et al. Proteomics. 2014 Jan.

Abstract

Proteolytic signaling, or regulated proteolysis, is an essential part of many important pathways such as Notch, Wnt, and Hedgehog. How the structure of the cleaved substrate regions influences the efficacy of proteolytic processing remains underexplored. Here, we analyzed the relative importance in proteolysis of various structural features derived from substrate sequences using a dataset of more than 5000 experimentally verified proteolytic events captured in CutDB. Accessibility to the solvent was recognized as an essential property of a proteolytically processed polypeptide chain. Proteolytic events were found nearly uniformly distributed among three types of secondary structure, although with some enrichment in loops. Cleavages in α-helices were found to be relatively abundant in regions apparently prone to unfolding, while cleavages in β-structures tended to be located at the periphery of β-sheets. Application of the same statistical procedures to proteolytic events divided into separate sets according to the catalytic classes of proteases proved consistency of the results and confirmed that the structural mechanisms of proteolysis are universal. The estimated prediction power of sequence-derived structural features, which turned out to be sufficiently high, presents a rationale for their use in bioinformatic prediction of proteolytic events.

Keywords: Bioinformatics; Cleavage site; Limited proteolysis; Protease; Proteolytic processing; Regulated proteolysis.

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References

    1. Barrett AJ, Rawlings ND, Woessner JM. Handbook of Proteolytic Enzymes: Cysteine, serine and threonine peptidases. Vol. 2. Elsevier Acad. Press; 2004.
    1. Turk B. Targeting proteases: successes, failures and future prospects. Nat Rev Drug Discov. 2006;5:785–799. - PubMed
    1. Turk B, Turk D, Turk V. Protease signalling: the cutting edge. EMBO J. 2012;31:1630–1643. - PMC - PubMed
    1. Lopez-Otin C, Overall CM. Protease degradomics: a new challenge for proteomics. Nat Rev Mol Cell Biol. 2002;3:509–519. - PubMed
    1. Quesada V, Ordóñez GR, Sánchez LM, Puente XS, López-Otín C. The Degradome database: mammalian proteases and diseases of proteolysis. Nucleic Acids Res. 2009;37:D239–43. - PMC - PubMed

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