1LCY

Crystal Structure of the Mitochondrial Serine Protease HtrA2

Summary for 1LCY

• Entry DOI: 10.2210/pdb1lcy/pdb
• Descriptor: HtrA2 serine protease (2 entities in total)
• Functional Keywords: apoptosis, serine protease, pdz domain, caspase activation, iap-binding, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Mitochondrion intermembrane space: O43464
• Total number of polymer chains: 1
• Total formula weight: 35001.82

Authors

Li, W.,Srinivasula, S.M.,Chai, J.,Li, P.,Wu, J.W.,Zhang, Z.,Alnemri, E.S.,Shi, Y. (deposition date: 2002-04-07, release date: 2002-05-22, Last modification date: 2024-02-14)

Primary citation

Li, W.,Srinivasula, S.M.,Chai, J.,Li, P.,Wu, J.W.,Zhang, Z.,Alnemri, E.S.,Shi, Y.
Structural insights into the pro-apoptotic function of mitochondrial serine protease HtrA2/Omi.
Nat.Struct.Biol., 9:436-441, 2002

PubMed Abstract: HtrA2/Omi, a mitochondrial serine protease in mammals, is important in programmed cell death. However, the underlining mechanism of HtrA2/Omi-mediated apoptosis remains unclear. Analogous to the bacterial homolog HtrA (DegP), the mature HtrA2 protein contains a central serine protease domain and a C-terminal PDZ domain. The 2.0 A crystal structure of HtrA2/Omi reveals the formation of a pyramid-shaped homotrimer mediated exclusively by the serine protease domains. The peptide-binding pocket of the PDZ domain is buried in the intimate interface between the PDZ and the protease domains. Mutational analysis reveals that the monomeric HtrA2/Omi mutants are unable to induce cell death and are deficient in protease activity. The PDZ domain modulates HtrA2/Omi-mediated cell death activity by regulating its serine protease activity. These structural and biochemical observations provide an important framework for deciphering the mechanisms of HtrA2/Omi-mediated apoptosis.

PubMed: 11967569
DOI: 10.1038/nsb795

Experimental method

X-RAY DIFFRACTION (2 Å)