Dissecting the Molecular Mechanism of Nucleotide-Dependent Activation of the KtrAB K+ Transporter

Andras Szollosi; Ricardo S Vieira-Pires; Celso M Teixeira-Duarte; Rita Rocha; João H Morais-Cabral

doi:10.1371/journal.pbio.1002356

Dissecting the Molecular Mechanism of Nucleotide-Dependent Activation of the KtrAB K+ Transporter

PLoS Biol. 2016 Jan 15;14(1):e1002356. doi: 10.1371/journal.pbio.1002356. eCollection 2016 Jan.

Authors

Andras Szollosi¹, Ricardo S Vieira-Pires¹, Celso M Teixeira-Duarte^{1

2}, Rita Rocha^{1

2}, João H Morais-Cabral^{1

2}

Affiliations

¹ IBMC, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
² Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.

Abstract

KtrAB belongs to the Trk/Ktr/HKT superfamily of monovalent cation (K+ and Na+) transport proteins that closely resemble K+ channels. These proteins underlie a plethora of cellular functions that are crucial for environmental adaptation in plants, fungi, archaea, and bacteria. The activation mechanism of the Trk/Ktr/HKT proteins remains unknown. It has been shown that ATP stimulates the activity of KtrAB while ADP does not. Here, we present X-ray structural information on the KtrAB complex with bound ADP. A comparison with the KtrAB-ATP structure reveals conformational changes in the ring and in the membrane protein. In combination with a biochemical and functional analysis, we uncover how ligand-dependent changes in the KtrA ring are propagated to the KtrB membrane protein and conclude that, despite their structural similarity, the activation mechanism of KtrAB is markedly different from the activation mechanism of K+ channels.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Triphosphate / metabolism*
Bacillus subtilis / metabolism*
Bacterial Proteins / chemistry
Bacterial Proteins / metabolism*
Cation Transport Proteins / chemistry
Cation Transport Proteins / metabolism*
Escherichia coli
Potassium / metabolism*
Protein Conformation

Substances

Bacterial Proteins
Cation Transport Proteins
KtrB protein, Bacteria
Adenosine Triphosphate
Potassium

Grants and funding

AS was supported by FEBS (Long term fellowship). This work was financially supported by national funds through FCT—Fundação para a Ciência e a Tecnologia/MEC—Ministério da Educação e Ciência and when applicable co-funded by FEDER funds within the Partnership Agreement PT2020 related with the research unit number 4293 and by FEDER funds through the Operational Competitiveness Program–COMPETE and by National Funds through FCT–Fundação para a Ciência e a Tecnologia under the project FCOMP-01-0124-FEDER-028115 (PTDC/BBB-BEP/2017/2012). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.