Amyloids are self-assembled protein architectures implicated in dozens of misfolding diseases. These assemblies appear to emerge through a "selection" of specific conformational "strains" which nucleate and propagate within cells to cause disease. The short Abeta(16-22) peptide, which includes the central core of the Alzheimer's disease Abeta peptide, generates an amyloid fiber which is morphologically indistinguishable from the full-length peptide fiber, but it can also form other morphologies under distinct conditions. Here we combine spectroscopic and microscopy analyses that reveal the subtle atomic-level differences that dictate assembly of two conformationally pure Abeta(16-22) assemblies, amyloid fibers and nanotubes, and define the minimal repeating unit for each assembly.

The structure of epothilone A, bound to alpha,beta-tubulin in zinc-stabilized sheets, was determined by a combination of electron crystallography at 2.89 angstrom resolution and nuclear magnetic resonance-based conformational analysis. The complex explains both the broad-based epothilone structure-activity relationship and the known mutational resistance profile. Comparison with Taxol shows that the longstanding expectation of a common pharmacophore is not met, because each ligand exploits the tubulin-binding pocket in a unique and independent manner.

The chemotherapeutic drug Taxol is known to interact within a specific site on ␤-tubulin. Although the general location of the site has been defined by photoaffinity labeling and electron crystallography, the original data were insufficient to make an absolute determination of the bound conformation. We have now correlated the crystallographic density with analysis of Taxol conformations and have found the unique solution to be a T-shaped Taxol structure. This T-shaped or butterfly structure is optimized within the ␤-tubulin site and exhibits functional similarity to a portion of the B9-B10 loop in the ␣-tubulin subunit. The model provides structural rationalization for a sizeable body of Taxol structureactivity relationship data, including binding affinity, photoaffinity labeling, and acquired mutation in human cancer cells.

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We present the crystal structure of the catalytic SET domain of G9a-like protein (GLP) in complex with BIX-01294. The inhibitor is bound in the substrate peptide groove at the location where the histone H3 residues (Lys4 to Arg8) N-terminal to the target lysine would occupy. The inhibitor is positioned in place by residues specific for G9a and GLP using planar stacking contacts, polar hydrogen bonds and van der Waals interactions.