“Protein aggregates associated with neurodegenerative disease have stubbornly resisted researchers’ efforts to get a good look at them. They refuse to crystallize well or yield to standard spectroscopic techniques. Now, advances in electron microscopy methods are forcing these molecules to give up their secrets. In the September 9 Nature, researchers led by David Eisenberg at the University of California, Los Angeles, and Tamir Gonen at the Howard Hughes Medical Institute’s Janelia Research Campus in Ashburn, Virginia, offer the closest look yet at the core of α-synuclein aggregates. The researchers made microscopic crystals from the peptides and used a relatively new technique called micro-electron diffraction to map them down to atomic resolution. Commenters called the work a tour de force.
‘[These] structures are the first to be determined by micro-electron diffraction from a molecule of previously unknown structure,’ noted Yifan Cheng at the University of California, San Francisco, in an accompanying Nature commentary. Others were similarly impressed. ‘To obtain a structure of this quality from a peptide material with such tiny crystals is a remarkable feat, and will probably serve as the model for many other studies,’ Gregory Petsko at Weill Cornell Medical College in New York told Alzforum. Tim Bartels at Brigham and Women’s Hospital, Boston, agreed, ‘The resolution here is unprecedented.’”