For one of OPIG’s short talks, I recently introduced the work done by Kotaro Tsuboyama et al. found in the paper A widespread family of heat-resistant obscure (Hero) proteins protect against protein instability and aggregation. As the name implies, HERO proteins have been found to retain function even after being boiled at 95C and have been found both in Drosophila and human HEK293T cell lines. Whilst it’s not impossible to find proteins which can “survive” 90+ Celsius, these are expected to be the reserve of extremophiles, not found in humans or fruit flies.
Continue readingTag Archives: Aggregation
Proteins evolve on the edge of supramolecular self-assembly
Inspired by Eoin’s interesting talks on prions and prion diseases, and Nick’s discussion of how Cyro-Electron microscopy is going to be the end of an era for Crystallography. I thought I’d look at a paper that discusses aggregation of protein complexes, with some cryo-electron microscopy thrown in for good measure.
a, A molecule gaining a single self-interacting patch forms a finite dimer. A self-interacting patch repeated on opposite sides of a symmetric molecule can result in infinite assembly. b, A point mutation in a dihedral octamer creates a new self-interacting patch (red), triggering assembly into a fibre.
Supramolecular assemblies are folded protein complexes forming into much larger units. This formation can be triggered by a mutation on a copy of the constituent homomers of the complex, acting as a self-interacting patch. If this patch were to form in a non-symmetric complex, it would likely form a finite assemble with a limited number of copies of the complex. However, if the complex has dihedral symmetry such that a patch is accessible at multiple separated locations, then complex can potentially form near infinite supramolecular assemblies. Continue reading