摘要
Chemoreceptor TlpB（Tlp=transducer-like protein）, which has been demonstrated to respond to pH sensing function, is crucial for the survival ofHelicobacterpylori（H, pylori） in host stomach. Urea was proposed to be essen- tial for TlpB＇s pH sensing function via binding with the Per-ARNT-Sim（PAS） domain of TlpB. Additionally, KI66R mutation of the TlpB protein has also been proven to have a similar effect on TlpB pH sensing as urea binding. Al- though X-ray crystallographic studies have been carried out for urea-bound Tlpl3, the molecular mechanism for the stabilization of TIpB induced by urea binding and K166R mutation remains to be elucidated. In this study, molecular dynamics simulations combined with principal component analysis（PCA） for the simulation results were used to gain an insight into the molecular mechanism of the stabilization of urea on TlpB protein. The formed H-bonds and salt-bridges surrounding Aspll4, which were induced by both urea binding and K166R mutation of TIpB, were im- portant to the stabilization of TlpB by urea. The similarity between the urea binding and K166R mutation as well as their differences in effect has been explicitly demonstrated with computer simulations at atomic-level. The findings may Dave the wav for the further researches of TlpB.
Chemoreceptor TlpB（Tlp=transducer-like protein）, which has been demonstrated to respond to pH sensing function, is crucial for the survival ofHelicobacterpylori（H, pylori） in host stomach. Urea was proposed to be essen- tial for TlpB＇s pH sensing function via binding with the Per-ARNT-Sim（PAS） domain of TlpB. Additionally, KI66R mutation of the TlpB protein has also been proven to have a similar effect on TlpB pH sensing as urea binding. Al- though X-ray crystallographic studies have been carried out for urea-bound Tlpl3, the molecular mechanism for the stabilization of TIpB induced by urea binding and K166R mutation remains to be elucidated. In this study, molecular dynamics simulations combined with principal component analysis（PCA） for the simulation results were used to gain an insight into the molecular mechanism of the stabilization of urea on TlpB protein. The formed H-bonds and salt-bridges surrounding Aspll4, which were induced by both urea binding and K166R mutation of TIpB, were im- portant to the stabilization of TlpB by urea. The similarity between the urea binding and K166R mutation as well as their differences in effect has been explicitly demonstrated with computer simulations at atomic-level. The findings may Dave the wav for the further researches of TlpB.
基金
Supported by the National Natural Science Foundation of China（No.21273095）.
