RESUMEN
Metal-binding peptides are versatile building blocks in supramolecular chemistry. We recently reported a class of crystalline materials formed through a combination of coiled-coil peptide self-association and metal coordination. Here, we probe the serendipitously discovered metal binding motif that drives the assembly and apply these insights to exert rational control over structure and morphology in the materials.
Asunto(s)
Metaloproteínas/química , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Cobre/química , Espectroscopía de Resonancia por Spin del Electrón/métodos , Metaloproteínas/síntesis química , Ingeniería de Proteínas/métodos , Multimerización de Proteína , Piridinas/químicaRESUMEN
Metal coordination and peptide-directed self-assembly are two proven methods for creating defined supramolecular architectures. Here, we report a new class of crystalline materials based on coiled-coil peptides bearing unnatural metal-chelating terpyridine moieties. High-resolution structural characterization of lattices formed in the presence of Cu2+ reveals a general assembly mechanism. Subtle sequence variation in the modular synthetic ligand dictates assembly morphology.
Asunto(s)
Complejos de Coordinación/química , Cobre/química , Péptidos/química , Polímeros/química , Complejos de Coordinación/síntesis química , Ligandos , Sustancias Macromoleculares , Modelos Moleculares , Estructura Molecular , Péptidos/síntesis químicaRESUMEN
We report here the comparison of five classes of unnatural amino acid building blocks for their ability to be accommodated into an α-helix in a protein tertiary fold context. High-resolution structural characterization and analysis of folding thermodynamics yield new insights into the relationship between backbone composition and folding energetics in α-helix mimetics and suggest refined design rules for engineering the backbones of natural sequences.
Asunto(s)
Proteínas/química , Secuencia de Aminoácidos , Datos de Secuencia Molecular , Pliegue de Proteína , Estructura Terciaria de Proteína , Homología de Secuencia de Aminoácido , TermodinámicaRESUMEN
Modular assembly of bio-inspired supramolecular polymers is a powerful technique to develop new soft nanomaterials, and protein folding is a versatile basis for preparing such materials. Previous work demonstrated a significant difference in the physical properties of closely related supramolecular polymers composed of building blocks in which identical coiled-coil-forming peptides are cross-linked by one of two subtly different organic linkers (one flexible and the other rigid). Herein, we investigate the molecular basis for this observation by isolating a single subunit of the supramolecular polymer chain and probing its structure and conformational flexibility by double electron-electron resonance (DEER) spectroscopy. Experimental spin-spin distance distributions for two different labeling sites coupled with molecular dynamics simulations provide insights into how the linker structure impacts chain dynamics in the coiled-coil supramolecular polymer.
