A self-compartmentalizing hexamer serine protease from Pyrococcus Horikoshii: Substrate selection achieved through multimerization

Karancsiné Menyhárd, Dóra and Kiss-Szemán, Anna and Tichy-Rács, Éva and Hornung, Balázs and Rádi, Krisztina and Szeltner, Zoltán and Domokos, Klarissza and Szamosi, Ilona and Náray-Szabó, Gábor and Polgár, László and Harmat, Veronika (2013) A self-compartmentalizing hexamer serine protease from Pyrococcus Horikoshii: Substrate selection achieved through multimerization. Journal of Biological Chemistry, 288 (24). pp. 17884-17894. ISSN 0021-9258 (print) 1083-351X (online)

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Abstract

Oligopeptidases impose a size limitation on their substrates, the mechanism of which has long been in debate. Here we present the structure of a hexameric serine protease, an oligopeptidase from Pyrococcus horikoshii (PhAAP), revealing a complex, self-compartmentalized inner space, where substrates may access the monomer active sites passing through a double-gated "check-in" system: first passing through a pore on the hexamer surface, then turning to enter through an even smaller opening at the monomers' domain-interface. This substrate screening strategy is unique within the family. We found that among oligopeptidases a member of catalytic apparatus is positioned near an amylogenic beta-edge, which needs to be protected to prevent aggregation and found different strategies applied to such end. We propose that self-assembly within the family results in characteristically different substrate selection mechanisms coupled to different multimerization states.

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