6I4L

Crystal Structure of Plasmodium falciparum actin I (G115A mutant) in the Mg-K-ATP/ADP state

6I4L の概要

• エントリーDOI: 10.2210/pdb6i4l/pdb
• 関連するPDBエントリー: 6I4D 6I4E 6I4F 6I4G 6I4H 6I4I 6I4J 6I4K
• 分子名称: Actin-1, Gelsolin, ADENOSINE-5'-TRIPHOSPHATE, ... (8 entities in total)
• 機能のキーワード: hydrolase, filamentous, glideosome, cytoskeleton, contractile protein
• 由来する生物種: Plasmodium falciparum (isolate 3D7); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 57428.63

構造登録者

Kumpula, E.-P.,Lopez, A.J.,Tajedin, L.,Han, H.,Kursula, I. (登録日: 2018-11-09, 公開日: 2019-06-26, 最終更新日: 2024-01-24)

主引用文献

Kumpula, E.P.,Lopez, A.J.,Tajedin, L.,Han, H.,Kursula, I.
Atomic view into Plasmodium actin polymerization, ATP hydrolysis, and fragmentation.
Plos Biol., 17:e3000315-e3000315, 2019

PubMed Abstract: Plasmodium actins form very short filaments and have a noncanonical link between ATP hydrolysis and polymerization. Long filaments are detrimental to the parasites, but the structural factors constraining Plasmodium microfilament lengths have remained unknown. Using high-resolution crystallography, we show that magnesium binding causes a slight flattening of the Plasmodium actin I monomer, and subsequent phosphate release results in a more twisted conformation. Thus, the Mg-bound monomer is closer in conformation to filamentous (F) actin than the Ca form, and this likely facilitates polymerization. A coordinated potassium ion resides in the active site during hydrolysis and leaves together with the phosphate, a process governed by the position of the Arg178/Asp180-containing A loop. Asp180 interacts with either Lys270 or His74, depending on the protonation state of the histidine, while Arg178 links the inner and outer domains (ID and OD) of the actin protomer. Hence, the A loop acts as a switch between stable and unstable filament conformations, the latter leading to fragmentation. Our data provide a comprehensive model for polymerization, ATP hydrolysis and phosphate release, and fragmentation of parasite microfilaments. Similar mechanisms may well exist in canonical actins, although fragmentation is much less favorable due to several subtle sequence differences as well as the methylation of His73, which is absent on the corresponding His74 in Plasmodium actin I.

PubMed: 31199804
DOI: 10.1371/journal.pbio.3000315

実験手法

X-RAY DIFFRACTION (1.83 Å)