Structure-function relationship of chimeric KdpFABC complex

Información del proyecto

KdpFABC

Identificador del acuerdo de subvención: 749732

DOI

10.3030/749732

Proyecto finalizado el 31 Mayo 2018

Fecha de la firma de la CE 17 Marzo 2017

Fecha de inicio 1 Agosto 2017

Fecha de finalización 31 Julio 2019

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 177 598,80

Aportación de la UE

€ 177 598,80

Coordinado por

RIJKSUNIVERSITEIT GRONINGEN
Netherlands

Periodic Reporting for period 1 - KdpFABC (Structure-function relationship of chimeric KdpFABC complex)

Período documentado: 2017-08-01 hasta 2019-07-31

Resumen del contexto y de los objetivos generales del proyecto

The structure-function relationships that explain the transport mechanism of membrane proteins on a molecular level are poorly understood and define one of the most complex and interdisciplinary research fields at the interface of Biology, Chemistry and Physics. The main objective of this project was to investigate the KdpFABC complex, a survival potassium uptake in bacteria. It combines features of three membrane transport systems (P-type ATPases, channels and ABC transporters), which traditionally are considered to be mechanistically and structurally distinct. A central question was to decipher the mechanism of action of the KdpFABC system, which is likely to overthrow the conceptual boundaries conventionally used to describe membrane transport mechanisms. The results might lead to a broader understanding of transport mechanism and to the design of novel antibiotics, as these systems are exclusively found in prokaryotes.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

During the period of the project we were able to obtain the structure of two distinct states of the protein complex by using the technique of high-resolution single particle cryo-electron microscopy. The new findings allowed to proposed a new mechanism of transport for the complex, which is so far unprecedented among other known mechanisms. Other than expected, not solely the channel-like subunit KdpA facilitates K+ translocation, but rather the combination of two joined half-channels formed by KdpA and KdpB, revealing a true chimera between a transporter and a channel. It demonstrates how in the course of evolution conserved protein architectures not only evolved from one another but can merge together to adapt to different environmental and cellular requirements.

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

Our results highlight a new mechanism of transport, which differs from what was postulated initially for this protein complex. We hope in the future to be able to describe the mechanism of action, the coupling between the subunits and the regulation of the complex in more detail. We aim to obtain further structures of the complex at different conformational states and contrast our findings to biochemical studies. Ultimately, we hope to encipher the equally simple and complex way by which membrane proteins complex operate. Our findings will not only have an impact on our general understanding of transport mechanism, but might provide the basis for the development of new bactericidal or bacteriostatic compounds.

New mechanism of transport in the KpdFABC complex