A proprotein convertase-inhibiting serpin with an ER targeting signal from Branchiostoma lanceolatum, a close relative of vertebrates

Bentele C, Krüger O, Tödtmann U, Oley M, Ragg H (2006)
Biochem. J. 395(3): 449-456.

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Lancelets are considered to take a key position in the evolution of lineages leading to vertebrates. Herein, a serpin from the lancelet Branchiostoma lanceolatum, Bl-Spn1, was identified that inhibits the PCs (proprotein convertases) PC1/3 and furin. The inhibitor forms SDS-stable complexes with either of its targets. Analysis of the inhibitor/furin reaction products by mass spectroscopy assigns the enzyme's cleavage position C-terminally to Met-Met-Lys-Arg downward arrow in the reactive site loop of Spn1, in concordance with the classical recognition/cleavage site of the principal vertebrate PCs. The inhibitor is equipped with a canonical ER (endoplasmic reticulum) retrieval signal, Lys-Asp-Glu-Leu (KDEL), marking the inhibitor as a guardian of the cellular secretory routes. Deletion of the ER retrieval signal results in the export of the inhibitor into the medium of transfected COS-7 cells, consistent with the assigned intracellular location. These results identify Bl-Spn1 as the first serpin that may inhibit PC1/3-like subtilases at their natural sites of action. Phylogenetic comparisons support a concept implying a general role for ER-residing serpins in the surveillance of subtilase-like enzymes along the constitutive and regulated secretory pathways of metazoans including a role in the defence of intruders that turn PCs to their propagation.
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Bentele C, Krüger O, Tödtmann U, Oley M, Ragg H. A proprotein convertase-inhibiting serpin with an ER targeting signal from Branchiostoma lanceolatum, a close relative of vertebrates. Biochem. J. 2006;395(3):449-456.
Bentele, C., Krüger, O., Tödtmann, U., Oley, M., & Ragg, H. (2006). A proprotein convertase-inhibiting serpin with an ER targeting signal from Branchiostoma lanceolatum, a close relative of vertebrates. Biochem. J., 395(3), 449-456.
Bentele, C., Krüger, O., Tödtmann, U., Oley, M., and Ragg, H. (2006). A proprotein convertase-inhibiting serpin with an ER targeting signal from Branchiostoma lanceolatum, a close relative of vertebrates. Biochem. J. 395, 449-456.
Bentele, C., et al., 2006. A proprotein convertase-inhibiting serpin with an ER targeting signal from Branchiostoma lanceolatum, a close relative of vertebrates. Biochem. J., 395(3), p 449-456.
C. Bentele, et al., “A proprotein convertase-inhibiting serpin with an ER targeting signal from Branchiostoma lanceolatum, a close relative of vertebrates”, Biochem. J., vol. 395, 2006, pp. 449-456.
Bentele, C., Krüger, O., Tödtmann, U., Oley, M., Ragg, H.: A proprotein convertase-inhibiting serpin with an ER targeting signal from Branchiostoma lanceolatum, a close relative of vertebrates. Biochem. J. 395, 449-456 (2006).
Bentele, Caterina, Krüger, Olaf, Tödtmann, Ulf, Oley, Mareke, and Ragg, Hermann. “A proprotein convertase-inhibiting serpin with an ER targeting signal from Branchiostoma lanceolatum, a close relative of vertebrates”. Biochem. J. 395.3 (2006): 449-456.
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