4EOY

Plasmodium falciparum Atg8 in complex with Plasmodium falciparum Atg3 peptide

Summary for 4EOY

• Entry DOI: 10.2210/pdb4eoy/pdb
• Descriptor: Microtubule-associated protein 1 light chain 3, Autophagy-related protein 3, CALCIUM ION, ... (7 entities in total)
• Functional Keywords: ubiquitin fold, transport protein
• Biological source: Plasmodium falciparum; More
• Cellular location: Cytoplasm (By similarity): C0H519
• Total number of polymer chains: 6
• Total formula weight: 48401.39

Authors

Hain, A.U.P.,Bosch, J. (deposition date: 2012-04-16, release date: 2013-02-20, Last modification date: 2024-04-03)

Primary citation

Hain, A.U.,Weltzer, R.R.,Hammond, H.,Jayabalasingham, B.,Dinglasan, R.R.,Graham, D.R.,Colquhoun, D.R.,Coppens, I.,Bosch, J.
Structural characterization and inhibition of the Plasmodium Atg8-Atg3 interaction.
J.Struct.Biol., 180:551-562, 2012

PubMed Abstract: The autophagy-related proteins are thought to serve multiple functions in Plasmodium and are considered essential to parasite survival and development. We have studied two key interacting proteins, Atg8 and Atg3, of the autophagy pathway in Plasmodium falciparum. These proteins are vital for the formation and elongation of the autophagosome and essential to the process of macroautophagy. Autophagy may be required for conversion of the sporozoite into erythrocytic-infective merozoites and may be crucial for other functions during asexual blood stages. Here we describe the identification of an Atg8 family interacting motif (AIM) in Plasmodium Atg3, which binds Plasmodium Atg8. We determined the co-crystal structure of PfAtg8 with a short Atg3¹⁰³⁻¹¹⁰ peptide, corresponding to this motif, to 2.2 Å resolution. Our in vitro interaction studies are in agreement with our X-ray crystal structure. Furthermore they suggest an important role for a unique Apicomplexan loop absent from human Atg8 homologues. Prevention of the protein-protein interaction of full length PfAtg8 with PfAtg3 was achieved at low micromolar concentrations with a small molecule, 1,2,3-trihydroxybenzene. Together our structural and interaction studies represent a starting point for future antimalarial drug discovery and design for this novel protein-protein interaction.

PubMed: 22982544
DOI: 10.1016/j.jsb.2012.09.001

Experimental method

X-RAY DIFFRACTION (2.22 Å)