8SK7

Cryo-EM structure of designed Influenza HA binder, HA_20, bound to Influenza HA (Strain: Iowa43)

8SK7 の概要

• エントリーDOI: 10.2210/pdb8sk7/pdb
• EMDBエントリー: 40557
• 分子名称: Hemagglutinin HA1 chain, Hemagglutinin, HA_20 minibinder (RFdiffusion-designed), ... (6 entities in total)
• 機能のキーワード: flu, influenza, hemagglutinin, ha, iowa43, ha_20, de novo protein, minibinder, binder, designed protein, fusion protein, glycoprotein, de novo protein-viral protein complex, de novo protein/viral protein
• 由来する生物種: Influenza A virus; 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 215503.28

構造登録者

Borst, A.J.,Bennett, N.R. (登録日: 2023-04-18, 公開日: 2023-06-14, 最終更新日: 2024-12-11)

主引用文献

Watson, J.L.,Juergens, D.,Bennett, N.R.,Trippe, B.L.,Yim, J.,Eisenach, H.E.,Ahern, W.,Borst, A.J.,Ragotte, R.J.,Milles, L.F.,Wicky, B.I.M.,Hanikel, N.,Pellock, S.J.,Courbet, A.,Sheffler, W.,Wang, J.,Venkatesh, P.,Sappington, I.,Torres, S.V.,Lauko, A.,De Bortoli, V.,Mathieu, E.,Ovchinnikov, S.,Barzilay, R.,Jaakkola, T.S.,DiMaio, F.,Baek, M.,Baker, D.
De novo design of protein structure and function with RFdiffusion.
Nature, 620:1089-1100, 2023

PubMed Abstract: There has been considerable recent progress in designing new proteins using deep-learning methods. Despite this progress, a general deep-learning framework for protein design that enables solution of a wide range of design challenges, including de novo binder design and design of higher-order symmetric architectures, has yet to be described. Diffusion models have had considerable success in image and language generative modelling but limited success when applied to protein modelling, probably due to the complexity of protein backbone geometry and sequence-structure relationships. Here we show that by fine-tuning the RoseTTAFold structure prediction network on protein structure denoising tasks, we obtain a generative model of protein backbones that achieves outstanding performance on unconditional and topology-constrained protein monomer design, protein binder design, symmetric oligomer design, enzyme active site scaffolding and symmetric motif scaffolding for therapeutic and metal-binding protein design. We demonstrate the power and generality of the method, called RoseTTAFold diffusion (RFdiffusion), by experimentally characterizing the structures and functions of hundreds of designed symmetric assemblies, metal-binding proteins and protein binders. The accuracy of RFdiffusion is confirmed by the cryogenic electron microscopy structure of a designed binder in complex with influenza haemagglutinin that is nearly identical to the design model. In a manner analogous to networks that produce images from user-specified inputs, RFdiffusion enables the design of diverse functional proteins from simple molecular specifications.

PubMed: 37433327
DOI: 10.1038/s41586-023-06415-8

実験手法

ELECTRON MICROSCOPY (2.93 Å)