The SAAS granin exhibits structural and functional homology to 7B2 and contains a highly potent hexapeptide inhibitor of PC1

FEBS Letters

Lindberg, Iris¹  Fortenberry, Yolanda¹  Cameron, Angus¹ 

[1] Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, 1901 Perdido St., New Orleans, LA 70112, USA

关键词: Prohormone convertase 1 and 2;    Furin;    SAAS granin;    7B2;    Inhibitor;    PC;    prohormone convertase;    pERTKR-MCA;    pGlu-Arg-Thr-Lys-Arg-methylcoumarinamide;    SAAS CT;    residues S219–P258 in intact mouse proSAAS;    SAAS Tyr0CT;    residues S219–P258 in intact mouse proSAAS with the addition of an N-terminal tyrosine;    SAAS CT1–24;    residues S219–R242 in intact mouse proSAAS;   

DOI  :  10.1016/S0014-5793(00)01511-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Prohormone convertases (PCs) 1 and 2 are thought to mediate the proteolytic cleavage of many peptide precursors. Endogenous inhibitors of both PC1 and PC2 have now been identified; the 7B2 protein is a nanomolar inhibitor of PC2, while the novel protein proSAAS was recently reported to be a micromolar inhibitor of PC1 [Fricker et al. (2000) J. Neurosci. 20, 639–648]. We here report evidence that 7B2 and proSAAS exhibit several elements of structural and functional homology. Firstly, 26 kDa human, mouse and rat proSAAS, like all vertebrate 7B2s, contain a proline-rich sequence within the first half of the molecule and also contain a C-terminal 40 residue peptide (SAAS CT peptide) separated from the remainder of the protein by a furin consensus sequence. The SAAS CT peptide contains the precise sequence of a hexapeptide previously identified by combinatorial peptide library screening as a potent inhibitor of PC1, and the vast majority of the inhibitory potency of proSAAS can be attributed to this hexapeptide. Further, like the 7B2 CT peptide, SAAS CT-derived peptides represent tight-binding competitive convertase inhibitors with nanomolar potencies. Lastly, recombinant PC1 is able to cleave the proSAAS CT peptide to a product with a mass consistent with cleavage following the inhibitory hexapeptide. Taken together, our results indicate that proSAAS and 7B2 may comprise two members of a functionally homologous family of convertase inhibitor proteins.

【 授权许可】

Unknown