6kos
Crystal structure of SUWA (Super WA20), a hyper-stable de novo protein with a dimeric bisecting topologyCrystal structure of SUWA (Super WA20), a hyper-stable de novo protein with a dimeric bisecting topology
Structural highlights
Publication Abstract from PubMedRecently, we designed and assembled protein nanobuilding blocks (PN-Blocks) from an intermolecularly folded dimeric de novo protein called WA20. Using this dimeric 4-helix bundle, we constructed a series of self-assembling supramolecular nanostructures including polyhedra and chain-type complexes. Here we describe the stabilization of WA20 by designing mutations that stabilize the helices and hydrophobic core. The redesigned proteins denature with substantially higher midpoints, with the most stable variant, called Super WA20 (SUWA), displaying an extremely high midpoint (Tm = 122 degrees C), much higher than the Tm of WA20 (75 degrees C). The crystal structure of SUWA reveals an intermolecularly folded dimer with bisecting U topology, similar to the parental WA20 structure, with two long alpha-helices of a protomer intertwined with the helices of another protomer. Molecular dynamics simulations demonstrate that the redesigned hydrophobic core in the center of SUWA significantly suppresses the deformation of helices observed in the same region of WA20, suggesting this is a critical factor stabilizing the SUWA structure. This hyperstable de novo protein is expected to be useful as nanoscale pillars of PN-Block components in new types of self-assembling nanoarchitectures. Hyperstable De Novo Protein with a Dimeric Bisecting Topology.,Kimura N, Mochizuki K, Umezawa K, Hecht MH, Arai R ACS Synth Biol. 2020 Jan 27. doi: 10.1021/acssynbio.9b00501. PMID:31951376[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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