Free Energy Landscape for the Entire Transport Cycle of Triose-Phosphate/Phosphate Translocator.

Authors:
Mizuki Takemoto
Mizuki Takemoto
Graduate School of Science
YongChan Lee
YongChan Lee
Memorial Sloan Kettering Cancer Center
Ryuichiro Ishitani
Ryuichiro Ishitani
Graduate School of Science
Cambridge | United States
Osamu Nureki
Osamu Nureki
Graduate School of Science
Cambridge | United States

Structure 2018 Sep 28;26(9):1284-1296.e4. Epub 2018 Jun 28.

Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Electronic address:

Secondary active transporters translocate their substrates using the electrochemical potentials of other chemicals and undergo large-scale conformational changes. Despite extensive structural studies, the atomic details of the transport mechanism still remain elusive. We performed a series of all-atom molecular dynamics simulations of the triose-phosphate/phosphate translocator (TPT), which exports organic phosphates in the chloroplast stroma in strict counter exchange with inorganic phosphate (P). Biased sampling methods, including the string method and umbrella sampling, successfully reproduced the conformational changes between the inward- and outward-facing states, along with the substrate binding. The free energy landscape of this entire TPT transition pathway demonstrated the alternating access and substrate translocation mechanisms, which revealed that P is relayed by positively charged residues along the transition pathway. Furthermore, the conserved Glu207 functions as a "molecular switch", linking the local substrate binding and the global conformational transition. Our results provide atomic-detailed insights into the substrate transport mechanism of the antiporter.

Abstract Video

Transporting phosphate


Source: Cell Press

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.str.2018.05.012DOI Listing

Still can't find the full text of the article?

We can help you send a request to the authors directly.
September 2018
162 Reads

Publication Analysis

Top Keywords

transition pathway
8
transport mechanism
8
substrate binding
8
triose-phosphate/phosphate translocator
8
landscape entire
8
conformational changes
8
energy landscape
8
free energy
8
stroma strict
4
charged residues
4
chloroplast stroma
4
phosphates chloroplast
4
residues transition
4
strict counter
4
counter exchange
4
positively charged
4
organic phosphates
4
inorganic phosphate
4
exchange inorganic
4
translocator tpt
4

Similar Publications