5CY5

Crystal structure of the T33-51H designed self-assembling protein tetrahedron

5CY5 の概要

• エントリーDOI: 10.2210/pdb5cy5/pdb
• 分子名称: T33-51H-B, T33-51H-A (2 entities in total)
• 機能のキーワード: bionanotechnology, symmetry, biomaterials, de novo protein, tetrahedral, computational design, rosetta, self-assembly, nanomaterial, solubility
• 由来する生物種: Thermoplasma acidophilum; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 40375.74

構造登録者

Cannon, K.A.,Cascio, D.,Park, R.,Boyken, S.,King, N.,Yeates, T.O. (登録日: 2015-07-30, 公開日: 2016-08-10, 最終更新日: 2023-09-27)

主引用文献

Cannon, K.A.,Park, R.U.,Boyken, S.E.,Nattermann, U.,Yi, S.,Baker, D.,King, N.P.,Yeates, T.O.
Design and structure of two new protein cages illustrate successes and ongoing challenges in protein engineering.
Protein Sci., 29:919-929, 2020

PubMed Abstract: In recent years, new protein engineering methods have produced more than a dozen symmetric, self-assembling protein cages whose structures have been validated to match their design models with near-atomic accuracy. However, many protein cage designs that are tested in the lab do not form the desired assembly, and improving the success rate of design has been a point of recent emphasis. Here we present two protein structures solved by X-ray crystallography of designed protein oligomers that form two-component cages with tetrahedral symmetry. To improve on the past tendency toward poorly soluble protein, we used a computational protocol that favors the formation of hydrogen-bonding networks over exclusively hydrophobic interactions to stabilize the designed protein-protein interfaces. Preliminary characterization showed highly soluble expression, and solution studies indicated successful cage formation by both designed proteins. For one of the designs, a crystal structure confirmed at high resolution that the intended tetrahedral cage was formed, though several flipped amino acid side chain rotamers resulted in an interface that deviates from the precise hydrogen-bonding pattern that was intended. A structure of the other designed cage showed that, under the conditions where crystals were obtained, a noncage structure was formed wherein a porous 3D protein network in space group I2 3 is generated by an off-target twofold homomeric interface. These results illustrate some of the ongoing challenges of developing computational methods for polar interface design, and add two potentially valuable new entries to the growing list of engineered protein materials for downstream applications.

PubMed: 31840320
DOI: 10.1002/pro.3802

実験手法

X-RAY DIFFRACTION (3.4 Å)