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Catching a pump in action

Molecular simulation insights into the mechanism of ABC transporter

Oeira, 18.05.10

It is not easy to catch a cellular pump in action. But researchers at the Protein Modeling and Molecular Simulation Labs used molecular simulation to understand how ATP hydrolysis might be linked to solute transport in the ATP-binding cassette (ABC) transporters, a superfamily of essential transmembrane proteins present in all living cells. Results were published in the Journal of Physical Chemistry.

ABC transporters can be thought of as molecular machines with two major components: the nucleotide binding domains (NBD), essentially the motor, and the transmembrane domains (TMD), the transporter itself. The long lasting question has been how does the motor transmit the energy released from ATP hydrolysis to the transporting part? By looking at molecular simulations of the NBDs, with ATP, ADP and phosphate, researchers at ITQB concluded that ATP hydrolysis induces conformational changes that affect the areas in contact with the TMDs, suggesting a possible signal transmission between the two parts of the machine.

Among other human conditions, ABC transporters are implicated in tumour resistance and cystic fibrosis, and have therefore received major attention from the scientific community. Recent crystallographic studies gave a good structural perspective of some ABC transporters but their static nature limited the understanding of the transporter’s mode of action. Molecular simulation presents itself as a viable alternative to deal with the dynamics of these large transmembrane proteins that otherwise would only be studied by indirect methods. In their work, ITQB researchers looked into the NBDs of a bacterial ABC transporter but the structure similarities found in the catalytic domain of this superfamily suggests a common mechanism of energy transduction powering the translocation, regardless of the transported substrate.


Original article

J. Phys. Chem. B 2010, 114, 5486–5496

Insights into the Molecular Mechanism of an ABC Transporter: Conformational Changes in the NBD Dimer of MJ0796

A. Sofia F. Oliveira, António M. Baptista, and Cláudio M. Soares


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