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

Dóra K. Menyhárd, Anna Kiss-Szemán, Éva Tichy-Rács, Balázs Hornung, Krisztina Rádi, Z. Szeltner, Klarissza Domokos, Ilona Szamosi, G. Náray-Szabó, L. Polgár, V. Harmat

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Oligopeptidases impose a size limitation on their substrates, the mechanism of which has long been under 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 and 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 residue of the catalytic apparatus is positioned near an amylogenic β-edge,whichneeds tobeprotected to prevent aggregation,andwe found that different oligopeptidases use different strategies to achieve such an end. We propose that self-assembly within the family results in characteristically different substrate selection mechanisms coupled to different multimerization states.

Original languageEnglish
Pages (from-to)17884-17894
Number of pages11
JournalJournal of Biological Chemistry
Volume288
Issue number24
DOIs
Publication statusPublished - Jun 14 2013

Fingerprint

Pyrococcus horikoshii
Serine Proteases
Substrates
Monomers
Self assembly
Catalytic Domain
Screening
Agglomeration
oligopeptidase

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

A self-compartmentalizing hexamer serine protease from Pyrococcus Horikoshii : Substrate selection achieved through multimerization. / Menyhárd, Dóra K.; Kiss-Szemán, Anna; Tichy-Rács, Éva; Hornung, Balázs; Rádi, Krisztina; Szeltner, Z.; Domokos, Klarissza; Szamosi, Ilona; Náray-Szabó, G.; Polgár, L.; Harmat, V.

In: Journal of Biological Chemistry, Vol. 288, No. 24, 14.06.2013, p. 17884-17894.

Research output: Contribution to journalArticle

Menyhárd, Dóra K. ; Kiss-Szemán, Anna ; Tichy-Rács, Éva ; Hornung, Balázs ; Rádi, Krisztina ; Szeltner, Z. ; Domokos, Klarissza ; Szamosi, Ilona ; Náray-Szabó, G. ; Polgár, L. ; Harmat, V. / A self-compartmentalizing hexamer serine protease from Pyrococcus Horikoshii : Substrate selection achieved through multimerization. In: Journal of Biological Chemistry. 2013 ; Vol. 288, No. 24. pp. 17884-17894.
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