Functional loop dynamics of the S-component of ECF transporter FolT

ABSTRACT

ECF (energy-coupling factor) transporters are responsible for many micronutrients uptake in organisms. The recently reported S-component structure of the ECF transporter FolT provides a solid basis to study the mechanism of the substrate folate binding. In this work, several kinds of molecular dynamics (MD) simulations methods are applied to investigate the dynamics of loops in folate-bound and folate-free state of FolT. Our study found: (1) The loops of the S-component play important roles and cooperate with each other in ligand binding process (namely, loop1, loop3 and loop5); (2) Although loop3 and loop5 are quite important in folate binding, our study showed that Loop1 is the dominant factor and serves as the gate controlling the folate binding and (3) The Steered molecular dynamics simulation shows evidence for a toppling working model proposed previously for the releasing process of the substrate folate.

GRAPHICAL ABSTRACT

KEYWORDS:

• ECF transporter
• loop dynamics
• FolT
• RAMD
• SMD

Acknowledgements

We thank the Supercomputer Center of East China Normal University for providing us computer time.

Disclosure statement

The authors declare no competing financial interest.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [grant nos. 21603144, 21433004, 91753103], Ministry of Science and Technology of China [grant no. 2016YFA0501700], Shanghai Sailing Program [grant no. 2016YF1408400], NYU Global Seed Grant, Shanghai Putuo District [grant 2014-A-02], Science and Technology Commission of Shanghai Municipality [grand no. 2016YF1408400, 2014-A-02], Shanghai Municipal Education Commission [grant no. 201701070005E00020].