Exchange, promiscuity, and orthogonality in designed coiled-coil peptide assemblies.

protein design is delivering new peptide and protein structures at a rapid pace. Many of these synthetic polypeptides form well-defined and hyperthermal-stable structures. Generally, however, less is known about the dynamic properties of the designed structures.

Structure and mechanism of the Zorya anti-phage defense system.

Zorya is a recently identified and widely distributed bacterial immune system that protects bacteria from viral (phage) infections. Three Zorya subtypes have been discovered, each containing predicted membrane-embedded ZorAB complexes paired with soluble subunits that differ among Zorya subtypes, notably ZorC and ZorD in type I Zorya systems. Here, we investigate the molecular basis of Zorya defense using cryo-electron microscopy, mutagenesis, fluorescence microscopy, proteomics, and functional studies.

Ion-driven rotary membrane motors: From structure to function.

Ion-driven membrane motors, essential across all domains of life, convert a gradient of ions across a membrane into rotational energy, facilitating diverse biological processes including ATP synthesis, substrate transport, and bacterial locomotion. Herein, we highlight recent structural advances in the understanding of two classes of ion-driven membrane motors: rotary ATPases and 5:2 motors. The recent structure of the human F-type ATP synthase is emphasised along with the gained structural insight into clinically relevant mutations.

Molecular Mechanism of STIL Coiled-Coil Domain Oligomerization.

Coiled-coil domains (CCDs) play key roles in regulating both healthy cellular processes and the pathogenesis of various diseases by controlling protein self-association and protein-protein interactions. Here, we probe the mechanism of oligomerization of a peptide representing the CCD of the STIL protein, a tetrameric multi-domain protein that is over-expressed in several cancers and associated with metastatic spread. STIL tetramerization is mediated both by an intrinsically disordered domain (STIL) and a structured CCD (STIL CCD).

Ion selectivity and rotor coupling of the Vibrio flagellar sodium-driven stator unit.

Bacteria swim using a flagellar motor that is powered by stator units. Vibrio spp. are highly motile bacteria responsible for various human diseases, the polar flagella of which are exclusively driven by sodium-dependent stator units (PomAB).

Differential sensing with arrays of de novo designed peptide assemblies.

Differential sensing attempts to mimic the mammalian senses of smell and taste to identify analytes and complex mixtures. In place of hundreds of complex, membrane-bound G-protein coupled receptors, differential sensors employ arrays of small molecules. Here we show that arrays of computationally designed de novo peptides provide alternative synthetic receptors for differential sensing.

Coiled coils 9-to-5: rational design of α-helical barrels with tunable oligomeric states.

The rational design of linear peptides that assemble controllably and predictably in water is challenging. Short sequences must encode unique target structures and avoid alternative states. However, the non-covalent forces that stabilize and discriminate between states are weak.

How Coiled-Coil Assemblies Accommodate Multiple Aromatic Residues.

Rational protein design requires understanding the contribution of each amino acid to a targeted protein fold. For a subset of protein structures, namely, α-helical coiled coils (CCs), knowledge is sufficiently advanced to allow the rational design of many structures, including entirely new protein folds. Current CC design rules center on using aliphatic hydrophobic residues predominantly to drive the folding and assembly of amphipathic α helices.