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Mylemans, B.

Publications and source records attributed to Mylemans, B..

2 recordsLinked to original sources

Crystal sturctures of Scone, pseudosymmetric folding of a symmetric designer protein

Recent years have seen a raise in the development of computational proteins including symmetric ones. We recently developed a nine-fold symmetric {beta}-propeller protein named Cake. Here we wanted to further engineer this protein to a three-fold symmetric nine-bladed propeller using computational design. Two nine-bladed propeller proteins were designed, named Scone-E and Scone-R. Crystallography however revealed the structure of both designs to adopt an eight-fold conformation with distorted termini, leading to a pseudo-symmetric protein. One of the proteins could only be crystallized upon addition of a polyoxometalate highlighting the usefulness of these molecules as a crystallisation additive.

systems biology↗

Structure and Stability of the designer protein WRAP-T and its permutants

{beta}-Propeller proteins are common natural disc-like pseudo-symmetric proteins that contain multiple repeats ( blades) each consisting of a 4-stranded anti-parallel {beta}-sheet. So far, 4- to 12-bladed {beta}-propellers have been discovered in nature showing large functional and sequential variation. Using computational design approaches, we created perfectly symmetric {beta}-propellers out of natural pseudo-symmetric templates. These proteins are useful tools to study protein evolution of this very diverse fold. While the 7-bladed architecture is the most common, no symmetric 7-bladed monomer has been created and characterized so far. Here we describe such a engineered protein, based on a highly symmetric natural template, and test the effects of circular permutation on its stability. Geometrical analysis of this protein and other artificial symmetrical proteins reveals no systematic constraint that could be used to help in engineering of this fold, and suggests sequence constraints unique to each {beta}-propeller sub-family.

biophysics↗