4EOY

Plasmodium falciparum Atg8 in complex with Plasmodium falciparum Atg3 peptide

4EOY の概要

• エントリーDOI: 10.2210/pdb4eoy/pdb
• 分子名称: Microtubule-associated protein 1 light chain 3, Autophagy-related protein 3, CALCIUM ION, ... (7 entities in total)
• 機能のキーワード: ubiquitin fold, transport protein
• 由来する生物種: Plasmodium falciparum; 詳細
• 細胞内の位置: Cytoplasm (By similarity): C0H519
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 48401.39

構造登録者

Hain, A.U.P.,Bosch, J. (登録日: 2012-04-16, 公開日: 2013-02-20, 最終更新日: 2024-04-03)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.22 Å)