3CJC

Actin dimer cross-linked by V. cholerae MARTX toxin and complexed with DNase I and Gelsolin-segment 1

3CJC の概要

• エントリーDOI: 10.2210/pdb3cjc/pdb
• 関連するPDBエントリー: 3CJB
• 分子名称: Actin, alpha skeletal muscle, Deoxyribonuclease-1, Gelsolin, ... (8 entities in total)
• 機能のキーワード: cross-linked dimer, atp-binding, cytoskeleton, methylation, muscle protein, nucleotide-binding, phosphoprotein, structural protein, actin-binding, apoptosis, endonuclease, glycoprotein, hydrolase, nuclease, nucleus, secreted, actin capping, alternative initiation, amyloid, disease mutation, structural protein-hydrolase complex, structural protein/hydrolase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 86849.47

構造登録者

Sawaya, M.R.,Kudryashov, D.S.,Pashkov, I.,Reisler, E.,Yeates, T.O. (登録日: 2008-03-12, 公開日: 2008-03-25, 最終更新日: 2020-07-29)

主引用文献

Kudryashov, D.S.,Durer, Z.A.,Ytterberg, A.J.,Sawaya, M.R.,Pashkov, I.,Prochazkova, K.,Yeates, T.O.,Loo, R.R.,Loo, J.A.,Satchell, K.J.,Reisler, E.
Connecting actin monomers by iso-peptide bond is a toxicity mechanism of the Vibrio cholerae MARTX toxin.
Proc.Natl.Acad.Sci.USA, 105:18537-18542, 2008

PubMed Abstract: The Gram-negative bacterium Vibrio cholerae is the causative agent of a severe diarrheal disease that afflicts three to five million persons annually, causing up to 200,000 deaths. Nearly all V. cholerae strains produce a large multifunctional-autoprocessing RTX toxin (MARTX(Vc)), which contributes significantly to the pathogenesis of cholera in model systems. The actin cross-linking domain (ACD) of MARTX(Vc) directly catalyzes a covalent cross-linking of monomeric G-actin into oligomeric chains and causes cell rounding, but the nature of the cross-linked bond and the mechanism of the actin cytoskeleton disruption remained elusive. To elucidate the mechanism of ACD action and effect on actin, we identified the covalent cross-link bond between actin protomers using limited proteolysis, X-ray crystallography, and mass spectrometry. We report here that ACD catalyzes the formation of an intermolecular iso-peptide bond between residues E270 and K50 located in the hydrophobic and the DNaseI-binding loops of actin, respectively. Mutagenesis studies confirm that no other residues on actin can be cross-linked by ACD both in vitro and in vivo. This cross-linking locks actin protomers into an orientation different from that of F-actin, resulting in strong inhibition of actin polymerization. This report describes a microbial toxin mechanism acting via iso-peptide bond cross-linking between host proteins and is, to the best of our knowledge, the only known example of a peptide linkage between nonterminal glutamate and lysine side chains.

PubMed: 19015515
DOI: 10.1073/pnas.0808082105

実験手法

X-RAY DIFFRACTION (3.9 Å)