2K7Z

Solution Structure of the Catalytic Domain of Procaspase-8

Summary for 2K7Z

• Entry DOI: 10.2210/pdb2k7z/pdb
• NMR Information: BMRB: 15932
• Descriptor: Caspase-8 (1 entity in total)
• Functional Keywords: caspase, apoptosis, initiator caspase, procaspase, cytoplasm, hydrolase, protease, thiol protease, zymogen
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 30345.42

Authors

Keller, N.,Zerbe, O.,Mares, J.,Gruetter, M.G. (deposition date: 2008-08-28, release date: 2009-03-24, Last modification date: 2024-05-08)

Primary citation

Keller, N.,Mares, J.,Zerbe, O.,Grutter, M.G.
Structural and biochemical studies on procaspase-8: new insights on initiator caspase activation.
Structure, 17:438-448, 2009

PubMed Abstract: Caspases are proteases with an active-site cysteine and aspartate specificity in their substrates. They are involved in apoptotic cell death and inflammation, and dysfunction of these enzymes is directly linked to a variety of diseases. Caspase-8 initiates an apoptotic pathway triggered by external stimuli. It was previously characterized in its active inhibitor bound state by crystallography. Here we present the solution structure of the monomeric unprocessed catalytic domain of the caspase-8 zymogen, procaspase-8, showing for the first time the position of the linker and flexibility of the active site forming loops. Biophysical studies of carefully designed mutants allowed disentangling dimerization and processing, and we could demonstrate lack of activity of monomeric uncleaved procaspase-8 and of a processed but dimerization-incompetent mutant. The data provide experimental support in so-far unprecedented detail, and reveal why caspase-8 (and most likely other initiator caspases) needs the dimerization platform during activation.

PubMed: 19278658
DOI: 10.1016/j.str.2008.12.019

Experimental method

SOLUTION NMR