论文题目: | Structure of an EIIC Sugar Transporter Trapped in an Inward-facing Conformation |
作者: | Ren Z, Lee J, Moosa MM, Nian Y, Hu L, Xu Z, McCoy JG, Ferreon ACM, Im W, Zhou M |
联系作者: | mzhou@bcm.edu |
发表年度: | 2018 |
DOI: | doi: 10.1073/pnas.1800647115 |
摘要: |
The phosphoenolpyruvate-dependent phosphotransferase system (PTS) transports sugar into bacteria and phosphorylates the sugarfor metabolic consumption. The PTS is important for the survival of bacteria and thus a potential target for antibiotics, but its mechanism of sugar uptake and phosphorylation remains unclear. The PTS is composed of multiple proteins, and the membrane-embedded Enzyme IIC (EIIC) component transports sugars across the membrane. Crystal structures of two members of the glucose superfamily of EIICs, bcChbC and bcMalT, were solved in the inward-facing and outward-facing conformations, and the structures suggest that sugar translocation could be achieved by movement of a structured domain that contains the sugar-binding site. However, different conformations have not been captured on the same transporter to allow precise description of the conformational changes. Here we present a crystal structure of bcMalT trapped in an inward-facing conformation by a mercury ion that bridges two strategically placed cysteine residues. The structure allows direct comparison of the outward- and inward-facing conformations and reveals a large rigid-body motion of the sugar-binding domain and other conformational changes that accompany the rigid-body motion. All-atom molecular dynamics simulations show that the inward-facing structure is stable with or without the cross-linking. The conformational changes were further validated by single-molecule F?ster resonance energy transfer (smFRET). Combined, these results establish the elevator-type mechanism of transport in the glucose superfamily of EIIC transporters |
刊物名称: | Proceedings of the National Academy of Sciences of the United States of America |
论文出处: | http://www.pnas.org/content/early/2018/05/16/1800647115.long |
影响因子: | 9.661(2016年) |