2F2F

Crystal structure of cytolethal distending toxin (CDT) from Actinobacillus actinomycetemcomitans

2F2F の概要

• エントリーDOI: 10.2210/pdb2f2f/pdb
• 分子名称: Cytolethal distending toxin A, Cytolethal distending toxin B, cytolethal distending toxin C, ... (4 entities in total)
• 機能のキーワード: cytolethal distending toxin, cdt, actinobacillus actinomycetemcomitans, oligomerization, stability and toxic activity, toxin
• 由来する生物種: Aggregatibacter actinomycetemcomitans; 詳細
• 細胞内の位置: Cell outer membrane ; Lipid- anchor : O87120
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 153585.79

構造登録者

Yamada, T.,Komoto, J.,Saiki, K.,Konishi, K.,Takusagawa, F. (登録日: 2005-11-16, 公開日: 2006-03-28, 最終更新日: 2024-10-16)

主引用文献

Yamada, T.,Komoto, J.,Saiki, K.,Konishi, K.,Takusagawa, F.
Variation of loop sequence alters stability of cytolethal distending toxin (CDT): crystal structure of CDT from Actinobacillus actinomycetemcomitans
Protein Sci., 15:362-372, 2006

PubMed Abstract: Cytolethal distending toxin (CDT) secreted by Actinobacillus actinomycetemcomitans induces cell cycle arrest of cultured cells in the G2 phase. The crystal structure of the natural form of A. actinomycetemcomitans DCT (aCDT) has been determined at 2.4 A resolution. aCDT is a heterotrimer consisting of the three subunits, aCdtA, aCdtB, and aCdtC. Two crystallographically independent aCDTs form a dimer through interactions of the aCdtB subunits. The primary structure of aCDT has 94.3% identity with that of Haemophilus ducreyi CDT (hCDT), and the structure of aCDT is quite similar to that of hCDT reconstituted from the three subunits determined recently. However, the molecular packings in the crystal structures of aCDT and hCDT are quite different. A careful analysis of molecular packing suggests that variation of the amino acid residues in a nonconserved loop (181TSSPSSPERRGY192 of aCdtB and 181NSSSSPPERRVY192 of hCdtB) is responsible for the different oligomerization of very similar CDTs. The loop of aCdtB has a conformation to form a dimer, while the loop conformation of hCdtB prevents hCDT from forming a dimer. Although dimerization of aCDT does not affect toxic activity, it changes the stability of protein. aCDT rapidly aggregates and loses toxic activity in the absence of sucrose in a buffered solution, while hCDT is stable and retains toxic activity. Another analysis of crystal structures of aCDT and hCDT suggests that the receptor contact area is in the deep groove between CdtA and CdtC, and the characteristic "aromatic patch" on CdtA.

PubMed: 16434747
DOI: 10.1110/ps.051790506

実験手法

X-RAY DIFFRACTION (2.4 Å)