6LH8

Structure of aerolysin-like protein (Bombina maxima)

6LH8 の概要

• エントリーDOI: 10.2210/pdb6lh8/pdb
• 分子名称: aerolysin-like protein (2 entities in total)
• 機能のキーワード: pore-forming, aerolysin, amphibian, secretion, toxin
• 由来する生物種: Bombina maxima
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 17500.66

構造登録者

Bian, X.L.,Wang, Q.Q.,Li, X.,Teng, M.Q.,Zhang, Y. (登録日: 2019-12-07, 公開日: 2020-06-10, 最終更新日: 2024-03-27)

主引用文献

Wang, Q.,Bian, X.,Zeng, L.,Pan, F.,Liu, L.,Liang, J.,Wang, L.,Zhou, K.,Lee, W.,Xiang, Y.,Li, S.,Teng, M.,Li, X.,Guo, X.,Zhang, Y.
A cellular endolysosome-modulating pore-forming protein from a toad is negatively regulated by its paralog under oxidizing conditions.
J.Biol.Chem., 295:10293-10306, 2020

PubMed Abstract: Endolysosomes are key players in cell physiology, including molecular exchange, immunity, and environmental adaptation. They are the molecular targets of some pore-forming aerolysin-like proteins (ALPs) that are widely distributed in animals and plants and are functionally related to bacterial toxin aerolysins. βγ-CAT is a complex of an ALP (BmALP1) and a trefoil factor (BmTFF3) in the firebelly toad (). It is the first example of a secreted endogenous pore-forming protein that modulates the biochemical properties of endolysosomes by inducing pore formation in these intracellular vesicles. Here, using a large array of biochemical and cell biology methods, we report the identification of BmALP3, a paralog of BmALP1 that lacks membrane pore-forming capacity. We noted that both BmALP3 and BmALP1 contain a conserved cysteine in their C-terminal regions. BmALP3 was readily oxidized to a disulfide bond-linked homodimer, and this homodimer then oxidized BmALP1 via disulfide bond exchange, resulting in the dissociation of βγ-CAT subunits and the elimination of biological activity. Consistent with its behavior , BmALP3 sensed environmental oxygen tension , leading to modulation of βγ-CAT activity. Interestingly, we found that this C-terminal cysteine site is well conserved in numerous vertebrate ALPs. These findings uncover the existence of a regulatory ALP (BmALP3) that modulates the activity of an active ALP (BmALP1) in a redox-dependent manner, a property that differs from those of bacterial toxin aerolysins.

PubMed: 32499370
DOI: 10.1074/jbc.RA120.013556

実験手法

X-RAY DIFFRACTION (1.729 Å)