6WI4

Caspases from Scleractinian Coral

Summary for 6WI4

• Entry DOI: 10.2210/pdb6wi4/pdb
• Descriptor: Caspase-3, ACE-DEVD inhibitor, ... (4 entities in total)
• Functional Keywords: caspase, coral apoptosis, functional divergence, substrate selection, card-caspase, cell cycle
• Biological source: Porites astreoides; More
• Total number of polymer chains: 5
• Total formula weight: 55463.97

Authors

Clark, A.C.,Swartz, P.D. (deposition date: 2020-04-08, release date: 2020-08-26, Last modification date: 2024-10-09)

Primary citation

Shrestha, S.,Tung, J.,Grinshpon, R.D.,Swartz, P.,Hamilton, P.T.,Dimos, B.,Mydlarz, L.,Clark, A.C.
Caspases from scleractinian coral show unique regulatory features.
J.Biol.Chem., 295:14578-14591, 2020

PubMed Abstract: Coral reefs are experiencing precipitous declines around the globe with coral diseases and temperature-induced bleaching being primary drivers of these declines. Regulation of apoptotic cell death is an important component in the coral stress response. Although cnidaria are known to contain complex apoptotic signaling pathways, similar to those in vertebrates, the mechanisms leading to cell death are largely unexplored. We identified and characterized two caspases each from , a disease-sensitive reef-building coral, and , a disease-resistant reef-building coral. The caspases are predicted homologs of the human executioner caspases-3 and -7, but OfCasp3a ( caspase-3a) and PaCasp7a ( caspase-7a), which we show to be DDases, contain an N-terminal caspase activation/recruitment domain (CARD) similar to human initiator/inflammatory caspases. OfCasp3b ( caspase-3b) and PaCasp3 ( caspase-3), which we show to be VDases, have short pro-domains, like human executioner caspases. Our biochemical analyses suggest a mechanism in coral which differs from that of humans, where the CARD-containing DDase is activated on death platforms but the protease does not directly activate the VDase. The first X-ray crystal structure of a coral caspase, of PaCasp7a determined at 1.57 Å resolution, reveals a conserved fold and an N-terminal peptide bound near the active site that may serve as a regulatory exosite. The binding pocket has been observed in initiator caspases of other species. These results suggest mechanisms for the evolution of substrate selection while maintaining common activation mechanisms of CARD-mediated dimerization.

PubMed: 32788218
DOI: 10.1074/jbc.RA120.014345

Experimental method

X-RAY DIFFRACTION (1.57 Å)