8E12

Homotrimeric variant of tcTRP9, BGL14

8E12 の概要

• エントリーDOI: 10.2210/pdb8e12/pdb
• 分子名称: BGL14 (2 entities in total)
• 機能のキーワード: de novo, computationally designed, designed, tandem repeat protein, ctrp, de novo protein
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 57762.50

構造登録者

Kibler, R.,Stoddard, B.L.,Kennedy, M.A. (登録日: 2022-08-09, 公開日: 2023-04-12, 最終更新日: 2025-10-29)

主引用文献

Kibler, R.D.,Lee, S.,Kennedy, M.A.,Wicky, B.I.M.,Lai, S.M.,Kostelic, M.M.,Carr, A.,Li, X.,Chow, C.M.,Nguyen, T.K.,Carter, L.,Wysocki, V.H.,Stoddard, B.L.,Baker, D.
Design of pseudosymmetric protein hetero-oligomers.
Nat Commun, 15:10684-10684, 2024

PubMed Abstract: Pseudosymmetric hetero-oligomers with three or more unique subunits with overall structural (but not sequence) symmetry play key roles in biology, and systematic approaches for generating such proteins de novo would provide new routes to controlling cell signaling and designing complex protein materials. However, the de novo design of protein hetero-oligomers with three or more distinct chains with nearly identical structures is a challenging unsolved problem because it requires the accurate design of multiple protein-protein interfaces simultaneously. Here, we describe a divide-and-conquer approach that breaks the multiple-interface design challenge into a set of more tractable symmetric single-interface redesign tasks, followed by structural recombination of the validated homo-oligomers into pseudosymmetric hetero-oligomers. Starting from de novo designed circular homo-oligomers composed of 9 or 24 tandemly repeated units, we redesigned the inter-subunit interfaces to generate 19 new homo-oligomers and structurally recombined them to make 24 new hetero-oligomers, including ABC heterotrimers, A2B2 heterotetramers, and A3B3 and A2B2C2 heterohexamers which assemble with high structural specificity. The symmetric homo-oligomers and pseudosymmetric hetero-oligomers generated for each system have identical or nearly identical backbones, and hence are ideal building blocks for generating and functionalizing larger symmetric and pseudosymmetric assemblies.

PubMed: 39695145
DOI: 10.1038/s41467-024-54913-8

実験手法

X-RAY DIFFRACTION (3 Å)