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Understanding the Interacting Mechanism For the Type III Secretion System Through Molecular Dynamics Simulations
Author(s) -
Yang Jing,
Gao Meng,
Huang Yongqi
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.631.48
Subject(s) - effector , chaperone (clinical) , secretion , type three secretion system , biology , cytosol , microbiology and biotechnology , protein folding , plasma protein binding , biophysics , chemistry , biochemistry , virulence , gene , medicine , pathology , enzyme
The type III secretion system is found in a large number of Gram‐negative bacterial pathogens. They are responsible for the delivery of effector proteins into the cytosol of host cells. It has been found that delivery of effector proteins depends on association with specific chaperones in the bacterial cytosol. The structures of effector/chaperone complex reveal that the chaperone forms a homo/heterodimer which the effector binds to. Upon binding with the chaperone, the intrinsically disordered effector protein forms an extended ordered conformation. Although the overall structures of the chaperones are similar, the structures of the effector proteins and interactions between the effectors and chaperones are rather different. In this work, the effector/chaperone interactions from Pseudomonas aeruginosa , Salmonella typhimurium , and Yersinia pestis were studied to compare their coupled folding‐binding mechanisms through molecular dynamics simulations. Although the sequence similarity among the effectors is very low, the interacting pattern and mechanism are similar. Our results showed that the hairpin structures from both terminuses were critical to stabilize the encounter complex. On the contrary, helices located at the central segment interacted with the chaperone when the binding free energy barrier was crossed. Therefore, preformation of central alpha‐helices has little effect on the association rate. However, interactions between central helices and the chaperone were critical for the complex stability. Our results provided new insights into the binding affinity and kinetics for effector/chaperone interactions. Support or Funding Information This work was supported by National Natural Science Foundation of China (Grant number: 21603121) and Hubei University of Technology. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .