An Adaptive Mutation in Enterococcus faecium LiaR Associated with Antimicrobial Peptide Resistance Mimics Phosphorylation and Stabilizes LiaR in an Activated State
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- 作者：Milya Davlieva1 ; Angel Tovar-Yanez1 ; Kimberly DeBruler1 ; Paul G. Leonard2 ; Michael R. Zianni3 ; Cesar A. Arias4 ; 5 ; 6 ; Yousif Shamoo1 ; shamoo@rice.edu" class="auth_mail" title="E-mail the corresponding author
- 关键词：DAP ; daptomycin ; RD ; receiver domain ; DBD ; DNA-binding domain ; SEQ ; sedimentation equilibrium analytical ultracentrifugation ; SV ; sedimentation velocity ; MW ; molecular weight ; HTH ; helix-turn-helix ; MST ; microscale thermophoresis ; FEM ; feature-enhanced map
- 刊名：Journal of Molecular Biology
- 出版年：2016
- 出版时间：6 November 2016
- 年：2016
- 卷：428
- 期：22
- 页码：4503-4519
- 全文大小：2068 K
文摘
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In clinical settings, non-susceptibility to DAP by E. faecium is correlated frequently with a mutation in LiaR of Trp73 to Cys.
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To elucidate the physicochemical basis for LiaR-mediated changes in DAP susceptibility, we used a combination of biophysical and structural approaches.
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Our study revealed that the adaptive mutation W73C, even in the absence of phosphorylation, activates LiaR to undergo a phosphorylation-like self-dimerization event that allows LiaR to recognize and activate upstream regulatory regions.