How to Build a Complex, Functional Propeller Protein, From Parts

Abstract

By combining ancestral sequence reconstruction and in vitro evolution, Smock et al. identified single motifs that assemble into a functional five-bladed β-propeller, and a likely route for conversion into the more complex, extant single chain fusion. Interestingly, although sequence diversification destabilized five-motif fusions, it also destabilized aggregation-prone intermediates, increasing the level of functional protein in vivo.

Keywords: beta-propeller; protein fold; repeat protein structure; sequence evolution.

Figure 1

Examples of structural diversity within extant β-propeller structures. Each propeller blade consists of four β-strands that can be connected in diverse ways. (A) DDB1, a subunit of a ubiquitin ligase, is composed of three seven-bladed propellers with different β-strand topologies [5], including the simplest ‘intact’ blade topology (green) and a ‘Velcro’ frame (blue). Both the green and blue propellers are inserted between β-strands of the first two blades of the remaining propeller (magenta), which follows the Velcro frame overall but includes additional topological complexity in the third blade. (B) The six-bladed propeller of the DNA gyrase A C-terminal domain [4] (orange). For propellers with consistent topological repeats, a single repeat is shown in a darker color to highlight the topology, with β-strands labeled a-b-c-d from N- to C-terminus.