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Making a fast ion transporter

An international team of researchers at Institute for Molecular Science in Japan and Max Planck Institute of Biophysics in Germany reveals an ion transport mechanism of sodium/proton antiporter by simulating its motion. Based on the simulations, they now design a faster transporter by making mutation on “gate” of the transporter.
 

Na+/H+ antiporters exchange sodium ions and protons across cellular membrane to control pH, ion concentrations and cell volume, which is linked to a wide spectrum of diseases from heart failure to autism. Researchers now design a faster Na+/H+ antiporter based on the simulations.

An international team of researchers, research associate professor Kei-ichi Okazaki at Institute for Molecular Science and groups of professors Gerhard Hummer and Werner Kühlbrandt at Max Planck Institute of Biophysics, revealed an ion transport mechanism of the archaeal Na+/H+ antiporter PaNhaP in atomic detail by molecular dynamics simulations. Based on the simulations, they discovered a pair of residues that serves as a gate to the ion-binding site. Furthermore, they found that a mutation weakening the gate makes the transporter twice as fast as the wild type. The work was published in Nature Communications on April 15, 2019.

“It was surprising that the mutation makes the transporter faster,” Okazaki says, “the speed-up suggests that the gate balances competing demands of fidelity and efficiency.” The gate was discovered through simulations where they applied a method called transition path sampling to overcome the enormous time-scale gap between seconds-scale ion exchange and microseconds simulations. The simulations captured the ion transporting events, which is not possible with conventional simulations.

“We would like to understand design principles of transporters, how they recognize their substrates and how they control transport speeds,” Okazaki says, “these mechanistic understandings can help develop drugs to cure transporter-related diseases in future.”
 


Information of the paper

Kei-ichi Okazaki, David Wöhlert, Judith Warnau, Hendrik Jung, Özkan Yildiz, Werner Kühlbrandt and Gerhard Hummer

Journal Name: Nature Communications

Journal Title: “Mechanism of the electroneutral sodium/proton antiporter PaNhaP from transition-path shooting”

DOI: 10.1038/s41467-019-09739-0
 

Research Group

Institute for Molecular Science, Myodaiji, Okazaki 444-8585, Aichi, Japan
Max Planck Institute of Biophysics, 60438 Frankfurt am Main, Germany
 

Financial Supports

Max Planck Society, the Frankfurt International Max Planck Research School
SFB 807 ‘Transport and communication across biological membranes’
Building of Consortia for the Development of Human Resources in Science and Technology, MEXT, Japan
JSPS KAKENHI Grant Number JP18H02415
 

Contact Person

Name: Kei-ichi Okazaki
Address: Institute for Molecular Science, Myodaiji, Okazaki 444-8585, Japan
TEL: +81-564-55-7303
E-mail: keokazaki_at_ims.ac.jp (Please replace the "_at_" with @)

Press contact:
Public Relations, Research Enhancement Strategy Office, Institute for Molecular Science, Natural Institutes of Natural Sciences
TEL: +81-564-55-7209
FAX: +81-564-55-7374
E-mail: press_at_ims.ac.jp (Please replace the "_at_" with @)