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

apoptosome

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. 

apoptosome notes
apaf-1 notes
apaf-1 notes

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.

composition sketch
composition sketch
composition sketch
composition sketch

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.

chimera assets
cinema4d assets

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.