Structural change

  • June 7, 2012
Structural change

Paul Robustelli co-authors paper on a study of protein structures linked to Alzheimer's.

Researchers have conducted a detailed study of the protein structures behind diseases including Parkinson’s and Alzheimer’s, which could open up new avenues for research and potential treatment.

The study, Structure of an Intermediate State in Protein Folding and Aggregation, is published in the current edition of the prestigious journal Science.

Gates Cambridge alumnus Paul Robustelli is a co-author and helped develop the technique for determining the structure of protein molecules used in the study during his PhD at the University of Cambridge.

The researchers looked in great detail at the changes that convert a normally soluble protein into an aggregation-prone amyloid precursor.

Ordered amyloid fibril protein aggregates are a hallmark of a class of human diseases that includes Parkinson’s and Alzheimer’s. How proteins assemble into these structures has been poorly understood up to now, but the change in structure is thought to play a direct role in disease.

The study reveals the structural changes that precede aggregation. The results were obtained through a combination of nuclear magnetic resonance (NMR) spectroscopy and computational algorithms that enabled visualisation of the aggregation-prone amyloid precursor, even though it appears so rarely that its characteristics cannot be measured directly by NMR.

The results give a detailed description of the position of each atom in the excited state.

Writing in the same issue of Science, David Eliezer from the Department of Biochemistry and Program in Structural Biology at Weill Cornell Medical College, says: “This study provides a view, at an unprecedented level of detail, into the structural changes that convert a normally soluble protein into an aggregation-prone precursor.”

Paul [2006] says the research is the result of work he conducted during his PhD in Chemistry at the University of Cambridge, in the lab of Michele Vendruscolo, with the support of a Gates Cambridge scholarship.

He states: “This research utilises a new technique that I developed during my PhD studies to determine the structures of protein molecules using only a limited amount experimental data, which was previously believed insufficient for determining the structures of molecules.  The technique was applied to characterise a transiently populated conformational state of a protein molecule which explains, in atomic detail, why the molecule can misfold, or “aggregate”, into a abnormal structural state that is known to be associated with a variety of diseases, including Alzheimer’s disease and Parkinson’s disease.”

The publication is the seventh to result from his research at Cambridge. Paul is currently a postdoctoral research fellow at Columbia University in New York.

Picture credit: worradmu AND www.freedigitalphotos.net

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