7UPP

Crystal structure of designed heterotrimeric assembly DHT03_2arm_A21/B21/C long

7UPP の概要

• エントリーDOI: 10.2210/pdb7upp/pdb
• 分子名称: DHT03 protein A, DHT03 protein B, DHT03 protein C (3 entities in total)
• 機能のキーワード: de novo designed protein, de novo protein
• 由来する生物種: synthetic construct; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 78962.24

構造登録者

Chang, Y.,Bhabha, G.,Ekiert, D.C. (登録日: 2022-04-16, 公開日: 2022-12-14, 最終更新日: 2024-04-03)

主引用文献

Bermeo, S.,Favor, A.,Chang, Y.T.,Norris, A.,Boyken, S.E.,Hsia, Y.,Haddox, H.K.,Xu, C.,Brunette, T.J.,Wysocki, V.H.,Bhabha, G.,Ekiert, D.C.,Baker, D.
De novo design of obligate ABC-type heterotrimeric proteins.
Nat.Struct.Mol.Biol., 29:1266-1276, 2022

PubMed Abstract: The de novo design of three protein chains that associate to form a heterotrimer (but not any of the possible two-chain heterodimers) and that can drive the assembly of higher-order branching structures is an important challenge for protein design. We designed helical heterotrimers with specificity conferred by buried hydrogen bond networks and large aromatic residues to enhance shape complementary packing. We obtained ten designs for which all three chains cooperatively assembled into heterotrimers with few or no other species present. Crystal structures of a helical bundle heterotrimer and extended versions, with helical repeat proteins fused to individual subunits, showed all three chains assembling in the designed orientation. We used these heterotrimers as building blocks to construct larger cyclic oligomers, which were structurally validated by electron microscopy. Our three-way junction designs provide new routes to complex protein nanostructures and enable the scaffolding of three distinct ligands for modulation of cell signaling.

PubMed: 36522429
DOI: 10.1038/s41594-022-00879-4

実験手法

X-RAY DIFFRACTION (3.35 Å)