Protein molecules have the ability to form a rich variety of natural and artificial structures and materials. We show that amyloid fibrils, ordered supramolecular nanostructures that are self-assembled from a wide range of polypeptide molecules, have rigidities varying over four orders of magnitude, and constitute a class of high-performance biomaterials. We elucidate the molecular origin of fibril material properties and show that the major contribution to their rigidity stems from a generic interbackbone hydrogen-bonding network that is modulated by variable side-chain interactions.

The cross-β amyloid form of peptides and proteins represents an archetypal and widely accessible structure consisting of ordered arrays of β-sheet filaments. These complex aggregates have remarkable chemical and physical properties, and the conversion of normally soluble functional forms of proteins into amyloid structures is linked to many debilitating human diseases, including several common forms of age-related dementia. Despite their importance, however, cross-β amyloid fibrils have proved to be recalcitrant to detailed structural analysis. By combining structural constraints from a series of experimental techniques spanning five orders of magnitude in length scale—including magic angle spinning nuclear magnetic resonance spectroscopy, X-ray fiber diffraction, cryoelectron microscopy, scanning transmission electron microscopy, and atomic force microscopy—we report the atomic-resolution (0.5 Å) structures of three amyloid polymorphs formed by an 11-residue peptide. These structures reveal the details of the packing interactions by which the constituent β-strands are assembled hierarchically into protofilaments, filaments, and mature fibrils.

HP1 family proteins are adaptor molecules, containing two related chromo domains that are required for chromatin packaging and gene silencing. Here we present the structure of the chromo shadow domain from mouse HP1β bound to a peptide containing a consensus PXVXL motif found in many HP1 binding partners. The shadow domain exhibits a novel mode of peptide recognition, where the peptide binds across the dimer interface, sandwiched in a β‐sheet between strands from each monomer. The structure allows us to predict which other shadow domains bind similar PXVXL motif‐containing peptides and provides a framework for predicting the sequence specificity of the others. We show that targeting of HP1β to heterochromatin requires shadow domain interactions with PXVXL‐containing proteins in addition to chromo domain recognition of Lys‐9‐methylated histone H3. Interestingly, it also appears to require the simultaneous recognition of two Lys‐9‐methylated histone H3 molecules. This finding implies a further complexity to the histone code for regulation of chromatin structure and suggests how binding of HP1 family proteins may lead to its condensation.

Membrane proteins pose a huge challenge for structural analysis, but a new study reports the first NMR structure determination of a detergent-solubilized seven-helical transmembrane (7TM) protein, the phototaxis receptor sensory rhodopsin II. This case study may open the doors to similar solution NMR structures for other 7TM proteins. Seven-helix membrane proteins represent a challenge for structural biology. Here we report the first NMR structure determination of a detergent-solubilized seven-helix transmembrane (7TM) protein, the phototaxis receptor sensory rhodopsin II (pSRII) from Natronomonas pharaonis, as a proof of principle. The overall quality of the structure ensemble is good (backbone r.m.s. deviation of 0.48 Å) and agrees well with previously determined X-ray structures. Furthermore, measurements in more native-like small phospholipid bicelles indicate that the protein structure is the same as in detergent micelles, suggesting that environment-specific effects are minimal when using mild detergents. We use our case study as a platform to discuss the feasibility of similar solution NMR studies for other 7TM proteins, including members of the family of G protein–coupled receptors.