- PDB-4mkq: Crystal structure of the Pore-Forming Toxin Monalysin mutant dele... -
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基本情報
登録情報
データベース: PDB / ID: 4mkq
タイトル
Crystal structure of the Pore-Forming Toxin Monalysin mutant deleted of the membrane-spanning domain
要素
MONALYSIN
Monalysin
キーワード
TOXIN / Pore-Forming Toxin
機能・相同性
機能・相同性情報
hemolysis in another organism / porin activity / pore complex / monoatomic ion transport / protein homooligomerization / toxin activity / host cell plasma membrane / extracellular region 類似検索 - 分子機能
ジャーナル: J Biol Chem / 年: 2015 タイトル: X-ray and Cryo-electron Microscopy Structures of Monalysin Pore-forming Toxin Reveal Multimerization of the Pro-form. 著者: Philippe Leone / Cecilia Bebeacua / Onya Opota / Christine Kellenberger / Bruno Klaholz / Igor Orlov / Christian Cambillau / Bruno Lemaitre / Alain Roussel / 要旨: β-Barrel pore-forming toxins (β-PFT), a large family of bacterial toxins, are generally secreted as water-soluble monomers and can form oligomeric pores in membranes following proteolytic cleavage ...β-Barrel pore-forming toxins (β-PFT), a large family of bacterial toxins, are generally secreted as water-soluble monomers and can form oligomeric pores in membranes following proteolytic cleavage and interaction with cell surface receptors. Monalysin has been recently identified as a β-PFT that contributes to the virulence of Pseudomonas entomophila against Drosophila. It is secreted as a pro-protein that becomes active upon cleavage. Here we report the crystal and cryo-electron microscopy structure of the pro-form of Monalysin as well as the crystal structures of the cleaved form and of an inactive mutant lacking the membrane-spanning region. The overall structure of Monalysin displays an elongated shape, which resembles those of β-pore-forming toxins, such as Aerolysin, but is devoid of a receptor-binding domain. X-ray crystallography, cryo-electron microscopy, and light-scattering studies show that pro-Monalysin forms a stable doughnut-like 18-mer complex composed of two disk-shaped nonamers held together by N-terminal swapping of the pro-peptides. This observation is in contrast with the monomeric pro-form of the other β-PFTs that are receptor-dependent for membrane interaction. The membrane-spanning region of pro-Monalysin is fully buried in the center of the doughnut, suggesting that upon cleavage of pro-peptides, the two disk-shaped nonamers can, and have to, dissociate to leave the transmembrane segments free to deploy and lead to pore formation. In contrast with other toxins, the delivery of 18 subunits at once, nearby the cell surface, may be used to bypass the requirement of receptor-dependent concentration to reach the threshold for oligomerization into the pore-forming complex.
AUTHORS STATE THAT PEPTIDE CHAINS (C AND D) AND PROTEIN CHAINS (A AND B) BELONG TO A SAME SINGLE ...AUTHORS STATE THAT PEPTIDE CHAINS (C AND D) AND PROTEIN CHAINS (A AND B) BELONG TO A SAME SINGLE CHAIN WITHOUT BEEN CLEAVED BETWEEN RESIDUES 35 AND 36. AUTHORS HAVE STRONG EVIDENCE OF THE DOMAIN SWAPPING BUT NO EXPERIMENTAL DATA COULD PERMIT TO ASSIGN THE CHAINS UNAMBIGUOUSLY. THEREFORE, THEY WERE ASSIGNED DISTINCT CHAIN IDS.
配列の詳細
THE SEQUENCE OF CHAIN C AND D MATCHES UNIPROT ENTRY Q1I8U1 BETWEEN RESIDUES 9 AND 35. THE SEQUENCE ...THE SEQUENCE OF CHAIN C AND D MATCHES UNIPROT ENTRY Q1I8U1 BETWEEN RESIDUES 9 AND 35. THE SEQUENCE OF CHAIN A AND B MATCHES UNIPROT ENTRY Q1I8U1 BETWEEN RESIDUES 36 AND 271, WITH A DELETION OF MEMBRANE SPANNING DOMAIN (RESIDUES 102-170), THAT IS REPLACED BY A GLY501-SER502 DIPEPTIDE LINKER. SEE REMARK 400 FOR CHAIN ID ASSIGNMENT DETAILS.