Aggregates of a protein called tau are associated with many neurological disorders, including Alzheimer’s disease. Two six-amino acid segments of tau, which form structural motifs called steric zippers between adjacent protein strands in fibrils, cause tau aggregation. Those segments go by the names VQIVYK and VQIINK for the one-letter abbreviations of their constituent amino acids. David S. Eisenberg and coworkers at the University of California, Los Angeles, solved the structure of VQIVYK a decade ago (Nature 2007, DOI: 10.1038/nature05695). VQIINK formed crystals too small for conventional X-ray diffraction. Now, using microelectron diffraction, which works with nanometer-sized crystals, Eisenberg, postdoc Paul M. Seidler, and coworkers have solved crystal structures of VQIINK (Nat. Chem. 2017, DOI: 10.1038/nchem.2889). The new VQIINK structure reveals that it is a more powerful driver of tau aggregation and forms a larger zipper interface between strands than VQIVYK. In addition, the researchers show that a 10-amino acid peptide containing VQIINK simultaneously forms two zipper interfaces with different parts of the segment, which helps account for the improved fibril formation of VQIINK. The six-residue segment on its own forms yet another zipper interface. The researchers used the new structures to design peptides that inhibit tau aggregation by blocking the various interfaces and capping the ends of the fibrils. Also, the inhibitors block full-length tau fibrils from entering cells, which means they may be able to prevent the spread of tau aggregation in the brain.