Forskning ved Københavns Universitet - Københavns Universitet


Crystal structures of human caspase 6 reveal a new mechanism for intramolecular cleavage self-activation

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  • Xiao Jun Wang
  • Qin Cao
  • Xiang Liu
  • Wang, Kaituo
  • Wei Mi
  • Yan Zhang
  • Lan Fen Li
  • Andrea C. Leblanc
  • Xiao Dong Su

Dimeric effectors caspase 3 and caspase 7 are activated by initiator caspase processing. In this study, we report the crystal structures of effector caspase 6 (CASP6) zymogen and N-Acetyl-Val-Glu-Ile-Asp-al-inhibited CASP6. Both of these forms of CASP6 have a dimeric structure, and in CASP6 zymogen the intersubunit cleavage site 190 TEVD 193 is well structured and inserts into the active site. This positions residue Asp 193 to be easily attacked by the catalytic residue Cys 163. We demonstrate biochemically that intramolecular cleavage at Asp 193 is a prerequisite for CASP6 self-activation and that this activation mechanism is dependent on the length of the L2 loop. Our results indicate that CASP6 can be activated and regulated through intramolecular self-cleavage.

TidsskriftEMBO Reports
Udgave nummer11
Sider (fra-til)841-847
Antal sider7
StatusUdgivet - 1 nov. 2010

ID: 234874581