Structural, physicochemical and dynamic features conserved within the aerolysin pore-forming toxin family

被引:39
作者
Cirauqui, Nuria [1 ,2 ]
Abriata, Luciano A. [1 ]
van der Goot, F. Gisou [3 ]
Dal Peraro, Matteo [1 ]
机构
[1] Ecole Polytech Fed Lausanne, Inst Bioengn, Sch Life Sci, CH-1015 Lausanne, Switzerland
[2] Univ Fed Rio de Janeiro, Dept Pharmaceut Biotechnol, BR-21941902 Rio De Janeiro, Brazil
[3] Ecole Polytech Fed Lausanne, Global Hlth Inst, Sch Life Sci, CH-1015 Lausanne, Switzerland
来源
SCIENTIFIC REPORTS | 2017年 / 7卷
关键词
PERFRINGENS EPSILON-TOXIN; CRYO-EM STRUCTURE; CRYSTAL-STRUCTURE; MOLECULAR-DYNAMICS; MEMBRANE-INSERTION; PROTEIN-STRUCTURE; REVEALS; RECEPTOR; RECOGNITION; COEVOLUTION;
D O I
10.1038/s41598-017-13714-4
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Aerolysin is the founding member of a major class of beta-pore-forming toxins (beta-PFTs) found throughout all kingdoms of life. PFTs are cytotoxic proteins produced as soluble monomers, which oligomerize at the membrane of target host cells forming pores that may lead to osmotic lysis and cell death. Besides their role in microbial infection, they have become interesting for their potential as biotechnological sensors and delivery systems. Using an approach that integrates bioinformatics with molecular modeling and simulation, we looked for conserved features across this large toxin family. The cell surface-binding domains present high variability within the family to provide membrane receptor specificity. On the contrary, the novel concentric double beta-barrel structure found in aerolysin is highly conserved in terms of sequence, structure and conformational dynamics, which likely contribute to preserve a common transition mechanism from the prepore to the mature pore within the family. Our results point to the key role of several amino acids in the conformational changes needed for oligomerization and further pore formation, such as Y221, W227, P248, Q263 and L277, which we propose are involved in the release of the stem loop and the two adjacent beta-strands to form the transmembrane beta-barrel.
引用
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页数:12
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