8C47

Leishmania ATP-actin monomer in complex with Leishmania profilin

8C47 の概要

• エントリーDOI: 10.2210/pdb8c47/pdb
• 分子名称: Profilin, Actin, GLYCEROL, ... (6 entities in total)
• 機能のキーワード: actin, profilin, leishmania, cytoskeleton, structural protein
• 由来する生物種: Leishmania major; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 58849.15

構造登録者

Kogan, K.,Kotila, T. (登録日: 2023-01-02, 公開日: 2024-03-06)

主引用文献

Vizcaino-Castillo, A.,Kotila, T.,Kogan, K.,Yanase, R.,Como, J.,Antenucci, L.,Michelot, A.,Sunter, J.D.,Lappalainen, P.
Leishmania profilin interacts with actin through an unusual structural mechanism to control cytoskeletal dynamics in parasites.
J.Biol.Chem., 300:105740-105740, 2024

PubMed Abstract: Diseases caused by Leishmania and Trypanosoma parasites are a major health problem in tropical countries. Because of their complex life cycle involving both vertebrate and insect hosts, and >1 billion years of evolutionarily distance, the cell biology of trypanosomatid parasites exhibits pronounced differences to animal cells. For example, the actin cytoskeleton of trypanosomatids is divergent when compared with other eukaryotes. To understand how actin dynamics are regulated in trypanosomatid parasites, we focused on a central actin-binding protein profilin. Co-crystal structure of Leishmania major actin in complex with L. major profilin revealed that, although the overall folds of actin and profilin are conserved in eukaryotes, Leishmania profilin contains a unique α-helical insertion, which interacts with the target binding cleft of actin monomer. This insertion is conserved across the Trypanosomatidae family and is similar to the structure of WASP homology-2 (WH2) domain, a small actin-binding motif found in many other cytoskeletal regulators. The WH2-like motif contributes to actin monomer binding and enhances the actin nucleotide exchange activity of Leishmania profilin. Moreover, Leishmania profilin inhibited formin-catalyzed actin filament assembly in a mechanism that is dependent on the presence of the WH2-like motif. By generating profilin knockout and knockin Leishmania mexicana strains, we show that profilin is important for efficient endocytic sorting in parasites, and that the ability to bind actin monomers and proline-rich proteins, and the presence of a functional WH2-like motif, are important for the in vivo function of Leishmania profilin. Collectively, this study uncovers molecular principles by which profilin regulates actin dynamics in trypanosomatids.

PubMed: 38340794
DOI: 10.1016/j.jbc.2024.105740

実験手法

X-RAY DIFFRACTION (2.2 Å)