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5wvc

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Structure of the CARD-CARD disk

Structural highlights

5wvc is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.993Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

APAF_HUMAN Oligomeric Apaf-1 mediates the cytochrome c-dependent autocatalytic activation of pro-caspase-9 (Apaf-3), leading to the activation of caspase-3 and apoptosis. This activation requires ATP. Isoform 6 is less effective in inducing apoptosis.^[1] ^[2]

Publication Abstract from PubMed

Death domain (DD)-fold assemblies play a crucial role in regulating the signaling to cell survival or death. Here we report the crystal structure of the caspase recruitment domain (CARD)-CARD disk of the human apoptosome. The structure surprisingly reveals that three 1:1 Apaf-1:procaspase-9 CARD protomers form a novel helical DD-fold assembly on the heptameric wheel-like platform of the apoptosome. The small-angle X-ray scattering and multi-angle light scattering data also support that three protomers could form an oligomeric complex similar to the crystal structure. Interestingly, the quasi-equivalent environment of CARDs could generate different quaternary CARD assemblies. We also found that the type II interaction is conserved in all DD-fold complexes, whereas the type I interaction is found only in the helical DD-fold assemblies. This study provides crucial insights into the caspase activation mechanism, which is tightly controlled by a sophisticated and highly evolved CARD assembly on the apoptosome, and also enables better understanding of the intricate DD-fold assembly.

Structural Insights into DD-Fold Assembly and Caspase-9 Activation by the Apaf-1 Apoptosome.,Su TW, Yang CY, Kao WP, Kuo BJ, Lin SM, Lin JY, Lo YC, Lin SC Structure. 2017 Mar 7;25(3):407-420. doi: 10.1016/j.str.2016.12.019. Epub 2017, Jan 19. PMID:28111022^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Hu Y, Benedict MA, Ding L, Nunez G. Role of cytochrome c and dATP/ATP hydrolysis in Apaf-1-mediated caspase-9 activation and apoptosis. EMBO J. 1999 Jul 1;18(13):3586-95. PMID:10393175 doi:10.1093/emboj/18.13.3586
↑ Ogawa T, Shiga K, Hashimoto S, Kobayashi T, Horii A, Furukawa T. APAF-1-ALT, a novel alternative splicing form of APAF-1, potentially causes impeded ability of undergoing DNA damage-induced apoptosis in the LNCaP human prostate cancer cell line. Biochem Biophys Res Commun. 2003 Jun 27;306(2):537-43. PMID:12804598
↑ Su TW, Yang CY, Kao WP, Kuo BJ, Lin SM, Lin JY, Lo YC, Lin SC. Structural Insights into DD-Fold Assembly and Caspase-9 Activation by the Apaf-1 Apoptosome. Structure. 2017 Mar 7;25(3):407-420. doi: 10.1016/j.str.2016.12.019. Epub 2017, Jan 19. PMID:28111022 doi:http://dx.doi.org/10.1016/j.str.2016.12.019