3E4C

Procaspase-1 zymogen domain crystal structure

Summary for 3E4C

• Entry DOI: 10.2210/pdb3e4c/pdb
• Related: 1RWX
• Descriptor: Caspase-1, MAGNESIUM ION (3 entities in total)
• Functional Keywords: zymogen, caspase-1, inflammasome, ice, caspase, il-1b, procaspase-1, procaspase, innate immunity, apoptosis, hydrolase, protease, thiol protease
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 67619.11

Authors

Elliott, J.M.,Rouge, L.,Wiesmann, C.,Scheer, J.M. (deposition date: 2008-08-11, release date: 2008-12-30, Last modification date: 2023-08-30)

Primary citation

Elliott, J.M.,Rouge, L.,Wiesmann, C.,Scheer, J.M.
Crystal structure of procaspase-1 zymogen domain reveals insight into inflammatory caspase autoactivation
J.Biol.Chem., 284:6546-6553, 2009

PubMed Abstract: One key event in inflammatory signaling is the activation of the initiator caspase, procaspase-1. Presented here is the crystal structure of the procaspase-1 zymogen without its caspase recruitment domain solved to 2.05 A. Although the isolated domain is monomeric in solution, the protein appeared dimeric in crystals. The loop arrangements in the dimer provide insight into the first autoproteolytic events that occur during activation by oligomerization. Additionally, in contrast to other caspases, we demonstrate that autoproteolysis at the second cleavage site, Asp316, is necessary for conversion to a stable dimer in solution. Critical elements of secondary structure are revealed in the crystal structure that explain why a dimeric protein is favored after proteolysis at this aspartic acid. Dimer stabilization is concurrent with a 130-fold increase in kcat, the sole contributing kinetic factor to an activated and efficient mediator of inflammation.

PubMed: 19117953
DOI: 10.1074/jbc.M806121200

Experimental method

X-RAY DIFFRACTION (2.05 Å)