1lcy
From Proteopedia
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Crystal Structure of the Mitochondrial Serine Protease HtrA2
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Parkinson disease 13 OMIM:[606441]
About this Structure
1LCY is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural insights into the pro-apoptotic function of mitochondrial serine protease HtrA2/Omi., Li W, Srinivasula SM, Chai J, Li P, Wu JW, Zhang Z, Alnemri ES, Shi Y, Nat Struct Biol. 2002 Jun;9(6):436-41. PMID:11967569
Page seeded by OCA on Thu Feb 21 13:43:55 2008
Categories: Homo sapiens | Single protein | Alnemri, E S. | Chai, J. | Li, P. | Li, W. | Shi, Y. | Srinivasula, S M. | Wu, J W. | Zhang, Z. | Apoptosis | Caspase activation | Iap-binding | Pdz domain | Serine protease
