The Apoptosome:
A Gatekeeper of Programmed Cell Death
Audience: Educated lay audience
Client: Prof. Derek Ng
An illustration that explains the activation of an apoptosome, and the structural changes that occur. The purpose of this project was to identify, collect, evaluate, synthesize, and integrate a variety of relevant data sources to create a well-informed, scientifically-accurate molecular illustration.
Format:
Print (editorial, magazine)
Tools used:
UCSF Chimera
Maxon Cinema 4D
Adobe Photoshop CC
Adobe Illustrator CC
Completed on:
April 2017
Research and data collection
For my research, I focused on retrieving structural data for Apaf-1, a monomer that oligomerizes to the heptameric ring of an apoptosome. Specifically, I was interested in its subunits and domains, and the structural changes that occur once it binds to cytochrome C and dATP.
Compositions
After the initial research stage, I explored several compositions that communicated different events of apoptosome formation. With guidance from Prof. Ng, I decided to illustrate the activation of Apaf-1 and the interaction between Apaf-1 subunits to assemble into the apoptosome.
PDB data
All PDB data were taken into Chimera. Protein sequences of Apaf-1 subunits were identified, along with any missing data. Assets were then exported into Photoshop for diagrammatic representations of structural information, and to Cinema 4D for 3D representations.
References: UniProtKB data: O14727 (APAF_HUMAN); UniProtKB data: P99999 (CYC_HUMAN); PDB data: 1Z6T – Apaf-1 (inactive); PDB data: 3J2T – human apoptosome and Apaf-1 (active); PDB data: 5JUY – human apoptosome and Apaf-1 (active); PDB data: 3ZCF – human cytochrome c; Cheng, T. C., Hong, C., Akey, I. V., Yuan, S., and C. W. Akey. A near atomic structure of the active human apoptosome. eLife. 2016; 5: 1-28. doi: 10.7554/eLife.17755.; Green, D. R. Apoptotic pathways: ten minutes to dead. Cell. 2005; 121:671-674. doi: 10.1016/j.cell.2005.05.019.; Riedl, S. J., Li, W., Chao, Y., Schwarzenbacher, R., and Y. Shi. Structure of the apoptotic protease-activating factor 1 bound to ADP. Nature. 2005; 434: 926-933. PubMed: 15829969; Yuan, S., Topf, M., Reubold, T. F., Eschenburg, S., and C. W. Akey. Changes in Apaf-1 conformation that drive apoptosome assembly. Biochemistry. 2013; 52 (13): 2319-2327. doi: 10.1021/bi301721g.; Zhou, M., Li, Y., Hu, Q., Bai, X., Huang, W., Yan, C., Scheres, S. H. W., and Y. Shi. Atomic structure of the apoptosome: mechanism of cytochrome c- and dATP-mediated activation of Apaf-1. Genes and development. 2015; 29: 2349-2361. doi: 10.1101/gad.272278.115.