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Chemical Biology

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Probes for protein structure


28 June 2006

Swedish scientists have demonstrated that a natural amino acid can be used to probe protein conformations.

Probing protein conformation
Lennart Johansson and colleagues from Umeň University used tryptophan (Trp) probes to study how mutation and folding affect the 3D structure of a bacterial protein. Johansson attached a synthetic fluorescent compound, BODIPY, at various sites in the protein. He showed that, when excited with light energy, tryptophan (Trp), or donor, residues in the protein can donate electronic energy to the BODIPY, or acceptor, groups.

The amount of energy transfer from a donor to an acceptor group depends on the distance between them. By measuring the energy transfer between the Trp and BODIPY groups Johansson was able to calculate how far apart the donor-acceptor pairs were.

A change in the distances between the donor-acceptor pairs indicated a change in the conformation of the protein; Trp-BODIPY pairs can be used to explore processes related to protein folding, explained Johansson. 'The approach might be applicable to the study of protein aggregation as, for example, in amyloid diseases such as Alzheimer's,' he said.

Johansson's team found that the structural information they obtained was in good agreement with x-ray data and molecular dynamics simulations for the same protein, demonstrating the accuracy of their method.

"The approach might be applicable to the study of protein aggregation as, for example, in amyloid diseases such as Alzheimer's"
Karl Jalkanen, an expert in spectroscopic methods used in biophysics from Curtin University of Technology in Perth, Australia said that it would be interesting to do further modelling work on the mechanism of energy transfer in this system. The donor-acceptor probe could be used 'not only in folding studies, but also in binding of substrates and other target molecules that have the probe attached,' said Jalkanen.

Katherine Vickers

References

M Olofsson, S Kalinin, J Zdunek, M Oliveberg and LB-┼ Johansson, Phys. Chem. Chem. Phys., 2006 
DOI: 10.1039/b601313a