8V9O

Imaging scaffold engineered to bind the therapeutic protein target BARD1

8V9O の概要

• エントリーDOI: 10.2210/pdb8v9o/pdb
• 分子名称: Tetrahedral Nanocage Cage, Non-Fusion Component, Tetrahedral Nanocage Cage Component Fused to Anti-BARD1 Darpin, CALCIUM ION (3 entities in total)
• 機能のキーワード: nanohedra, protein cage, tetrahedral, darpin, imaging scaffold, de novo protein
• 由来する生物種: synthetic construct; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 165799.14

構造登録者

Agdanowski, M.P.,Castells-Graells, R.,Sawaya, M.R.,Yeates, T.O.,Arbing, M.A. (登録日: 2023-12-08, 公開日: 2024-05-15, 最終更新日: 2024-06-12)

主引用文献

Agdanowski, M.P.,Castells-Graells, R.,Sawaya, M.R.,Cascio, D.,Yeates, T.O.,Arbing, M.A.
X-ray crystal structure of a designed rigidified imaging scaffold in the ligand-free conformation.
Acta Crystallogr.,Sect.F, 80:107-115, 2024

PubMed Abstract: Imaging scaffolds composed of designed protein cages fused to designed ankyrin repeat proteins (DARPins) have enabled the structure determination of small proteins by cryogenic electron microscopy (cryo-EM). One particularly well characterized scaffold type is a symmetric tetrahedral assembly composed of 24 subunits, 12 A and 12 B, which has three cargo-binding DARPins positioned on each vertex. Here, the X-ray crystal structure of a representative tetrahedral scaffold in the apo state is reported at 3.8 Å resolution. The X-ray crystal structure complements recent cryo-EM findings on a closely related scaffold, while also suggesting potential utility for crystallographic investigations. As observed in this crystal structure, one of the three DARPins, which serve as modular adaptors for binding diverse `cargo' proteins, present on each of the vertices is oriented towards a large solvent channel. The crystal lattice is unusually porous, suggesting that it may be possible to soak crystals of the scaffold with small (≤30 kDa) protein cargo ligands and subsequently determine cage-cargo structures via X-ray crystallography. The results suggest the possibility that cryo-EM scaffolds may be repurposed for structure determination by X-ray crystallography, thus extending the utility of electron-microscopy scaffold designs for alternative structural biology applications.

PubMed: 38767964
DOI: 10.1107/S2053230X2400414X

実験手法

X-RAY DIFFRACTION (3.81 Å)