<br/>Since the development of sequencing and X-ray crystallography techniques the primary, secondary, tertiary and quaternary structure of many proteins has been determined but how the primary sequence leads to the higher-level structures of the proteins is still, in many cases, unknown. The coiled-coil motif consists of two α helixes, secondary structures, that wrap around each other forming a helix of helices, or a coiled-coil. The coiled-coil structure is an outlier in that its sequence-structure relationship has been well studied and is well defined. We have designed four peptides based on a sequence known to form very stable coiled-coil structures (H30). The three additional sequences contain destabilizing mutations, L24V, L31V, and L24,31V. These perturbations to the stable coiled-coil, H30, were carefully chosen to allow for determination of how mutations to different regions of the sequence affect the thermodynamic stability of the system as well as if these mutations affect the system in an additive fashion and if the effect depends on the position within the sequence. The peptides in these experiments have an auto-quenching fluorophore, TAMRA, attached to the N-terminus allowing for the use of fluorescence spectrometry to study the thermodynamic stability of the coiled-coils. This fundamental research is required for the de novo design of coiled-coil systems with highly specific thermodynamic properties, like the ability of the coiled-coil to separate at specific temperatures. De novo design of proteins with specialized functions is important for the development of protein-based drugs and biologics, which make up a growing portion of the drugs being brought onto the market by the FDA, 29% in 2018.

Coiled-coils and sequence dependent thermal stability

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.