6KOS

Crystal structure of SUWA (Super WA20), a hyper-stable de novo protein with a dimeric bisecting topology

6KOS の概要

• エントリーDOI: 10.2210/pdb6kos/pdb
• 関連するPDBエントリー: 3VJF
• 分子名称: SUWA (Super WA20) (2 entities in total)
• 機能のキーワード: thermostable protein design, de novo protein, binary patterned design, four helix bundle, 3d domain swapping, bisecting u topology
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 50169.04

構造登録者

Kimura, N.,Arai, R. (登録日: 2019-08-13, 公開日: 2020-01-29, 最終更新日: 2023-11-22)

主引用文献

Kimura, N.,Mochizuki, K.,Umezawa, K.,Hecht, M.H.,Arai, R.
HyperstableDe NovoProtein with a Dimeric Bisecting Topology.
Acs Synth Biol, 9:254-259, 2020

PubMed Abstract: Recently, we designed and assembled protein nanobuilding blocks (PN-Blocks) from an intermolecularly folded dimeric 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 ( = 122 °C), much higher than the of WA20 (75 °C). The crystal structure of SUWA reveals an intermolecularly folded dimer with bisecting U topology, similar to the parental WA20 structure, with two long α-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 protein is expected to be useful as nanoscale pillars of PN-Block components in new types of self-assembling nanoarchitectures.

PubMed: 31951376
DOI: 10.1021/acssynbio.9b00501

実験手法

X-RAY DIFFRACTION (2 Å)