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| Structural insights into the pro-apoptotic function of mitochondrial serine protease HtrA2/Omi |
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| Author(s): Li WY, Srinivasula SM, Chai JJ, Li PW, Wu JW, Zhang ZJ, Alnemri ES, Shi YG |
| Source: NATURE STRUCTURAL BIOLOGY Volume: 9 Issue: 6 Pages: 436-441 Published: JUN 2002 |
| Times Cited: 133 References: 32 |
| Abstract: HtrA2/Omi, a mitchondrial 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 Angstrom 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Shi, YG (reprint author), Princeton Univ, Lewis Thomas Lab, Dept Mol Biol, Princeton, NJ 08544 USA |
Addresses:
1. Princeton Univ, Lewis Thomas Lab, Dept Mol Biol, Princeton, NJ 08544 USA
2. Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA |
| Publisher: NATURE AMERICA INC, 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA |
| Subject Category: Biochemistry & Molecular Biology; Biophysics; Cell Biology |
| IDS Number: 556XP |
| ISSN: 1072-8368 |
| DOI: 10.1038/nsb795 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |