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NARC-1/PCSK9 and Its Natural Mutants

Benjannet, Suzanne, Rhainds, David, Essalmani, Rachid, Mayne, Janice, Wickham, Louise, Jin, Weijun, Asselin, Marie-Claude, Hamelin, Josée, Varret, Mathilde, Allard, Delphine, Trillard, Mélanie, Abifadel, Marianne, Tebon, Angie, Attie, Alan D., Rader, Daniel J., Boileau, Catherine, Brissette, Louise, Chrétien, Michel, Prat, Annik, Seidah, Nabil G.·2004·Journal of Biological Chemistry
DOI 10.1074/jbc.m409699200
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  • The proteolytic activity of PCSK9 requires a catalytic triad of Asp186, His226, and Ser386.

    “The proteolytic activity of PCSK9 requires a triad of residues (Asp 186, His 226 and Ser 386), which constitute the 'catalytic triad' of the protease.”

    From PCSK9 is required for the disposal of non-acetylated intermediates of the nascent membrane protein BACE1 (2008) · cites this paper as Benjannet et al, 2004

    The Fig. 1 caption (page unavailable) identifies Asp, His, and Ser as PCSK9 active-site residues. The zymogen-processing results identify H226A as an active-site mutant that is not cleaved. Our copy does not identify the other two residues as Asp186 and Ser386 or establish that all three specified positions are required for proteolytic activity. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • PCSK9 is synthesized as an approximately 75 kDa proprotein (proPCSK9, P-form), and its N-terminal prodomain is removed by autocatalysis generating an approximately 65 kDa C-form that is secreted.

    “PCSK9 is synthesized as an approximately 75 kDa proprotein (proPCSK9, P-form); the N-terminal prodomain is then removed by autocatalysis (Seidah et al, 2003;Benjannet et al, 2004) generating an approximately 65 kDa form (C-form) that is secreted into the extracellular milieu (Grozdanov et al, 2006).”

    From PCSK9 is required for the disposal of non-acetylated intermediates of the nascent membrane protein BACE1 (2008) · cites this paper as Benjannet et al, 2004

  • Mutation of one residue of the PCSK9 catalytic triad abolishes its proteolytic activity and its ability to undergo processing to the C-form.

    “Mutation of one of these residues abolishes the proteolytic activity of PCSK9 and its ability to undergo processing to the C-form (Benjannet et al, 2004(Benjannet et al, , 2006;;McNutt et al, 2007).”

    From PCSK9 is required for the disposal of non-acetylated intermediates of the nascent membrane protein BACE1 (2008) · cites this paper as Benjannet et al, 2004

  • PCSK9 is synthesized as a proprotein zymogen in the ER that undergoes intramolecular autocatalytic cleavage to release the mature protein for transport out of the ER and for secretion.

    “PCSK9 is synthesized as a proprotein zymogen in the ER that undergoes intramolecular autocatalytic cleavage to release the mature protein for transport out of the ER and for secretion115–117.”

    From Pathways and Molecular Mechanisms Governing LDL Receptor Regulation (2025) · cites this paper as [117]

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Metadata

Authors
Benjannet, S., Rhainds, D., Essalmani, R., Mayne, J., Wickham, L., Jin, W., Asselin, M.-C., Hamelin, J., Varret, M., Allard, D., Trillard, M., Abifadel, M., Tebon, A., Attie, A. D., Rader, D. J., Boileau, C., Brissette, L., Chrétien, M., Prat, A., & Seidah, N. G.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2004-11
Volume
279
Issue
47
Pages
48865-48875
ISSN
0021-9258
DOI
10.1074/jbc.m409699200
Cited by
587
References
1
Language
en
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