3VBZ

Crystal structure of Taipoxin beta subunit isoform 2

3VBZ の概要

• エントリーDOI: 10.2210/pdb3vbz/pdb
• 関連するPDBエントリー: 3VC0
• 分子名称: Phospholipase A2 homolog, taipoxin beta chain (2 entities in total)
• 機能のキーワード: phospholipase a2 fold, pla2 fold, neurotoxin, phospholipase, calcium binding, taipoxin alpha subunit binding, taipoxin gamma subunit binding, secreted, toxin
• 由来する生物種: Oxyuranus scutellatus scutellatus (Australian taipan)
• 細胞内の位置: Secreted: P00615
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 26654.07

構造登録者

Cendron, L.,Micetic, I.,Polverino, P.,Beltramini, M.,Paoli, M. (登録日: 2012-01-03, 公開日: 2012-07-25, 最終更新日: 2023-09-13)

主引用文献

Cendron, L.,Micetic, I.,Polverino de Laureto, P.,Paoli, M.
Structural analysis of trimeric phospholipase A(2) neurotoxin from the Australian taipan snake venom.
Febs J., 279:3121-3135, 2012

PubMed Abstract: Snake pre-synaptic neurotoxins endowed with phospholipase A(2) activity are potent inducers of paralysis through the specific disruption of the neuromuscular junction pre-synaptic membrane and represent a valuable tool for investigating neuronal degeneration and recovery. They have different structural complexity and a wide range of lethal potency and enzymatic activity, although they share a similar mechanism of action. Although no correlation has been reported between neurotoxicity and enzymatic activity, toxicity increases with structural complexity and phospholipase A(2) oligomers show 10-fold lower LD(50) values compared to their monomeric counterparts. To date, no structural study has been performed on multimeric SPANs with the aim of shedding light on the correlation between structural complexity and neurotoxicity. In the present study, we investigated the structure of taipoxin, a trimeric phospholipase A(2) neurotoxin, as well as that of its subunits, by X-ray crystallography and small angle X-ray scattering analysis. We present the high-resolution structure of two isoforms of the taipoxin β subunit, which show no neurotoxic activity but enhance the activity of the other subunits in the complex. One isoform shows no structural change that could justify the lack of activity. The other displays three point mutations in critical positions for the catalytic activity. Moreover, we designed a model for the quaternary structure of taipoxin under physiological conditions, in which the three subunits are organized into a flat holotoxin with the substrate binding sockets exposed on the same side of the complex, which suggests a role for this interface in the toxin-membrane interaction.

PubMed: 22776098
DOI: 10.1111/j.1742-4658.2012.08691.x

実験手法

X-RAY DIFFRACTION (1.76 Å)