6WRW

Crystal structure of computationally designed protein 2DS25.5 in complex with the human Transferrin receptor ectodomain

6WRW の概要

• エントリーDOI: 10.2210/pdb6wrw/pdb
• 分子名称: Transferrin receptor protein 1, Computationally designed protein 2DS25.5, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: complex, beta sheet, receptor, de novo protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 167240.80

構造登録者

Abraham, J.,Coscia, A.,Olal, D.,Sahtoe, D.D.,Baker, D.,Clark, L. (登録日: 2020-04-30, 公開日: 2021-04-28, 最終更新日: 2024-10-16)

主引用文献

Sahtoe, D.D.,Coscia, A.,Mustafaoglu, N.,Miller, L.M.,Olal, D.,Vulovic, I.,Yu, T.Y.,Goreshnik, I.,Lin, Y.R.,Clark, L.,Busch, F.,Stewart, L.,Wysocki, V.H.,Ingber, D.E.,Abraham, J.,Baker, D.
Transferrin receptor targeting by de novo sheet extension.
Proc.Natl.Acad.Sci.USA, 118:-, 2021

PubMed Abstract: The de novo design of polar protein-protein interactions is challenging because of the thermodynamic cost of stripping water away from the polar groups. Here, we describe a general approach for designing proteins which complement exposed polar backbone groups at the edge of beta sheets with geometrically matched beta strands. We used this approach to computationally design small proteins that bind to an exposed beta sheet on the human transferrin receptor (hTfR), which shuttles interacting proteins across the blood-brain barrier (BBB), opening up avenues for drug delivery into the brain. We describe a design which binds hTfR with a 20 nM , is hyperstable, and crosses an in vitro microfluidic organ-on-a-chip model of the human BBB. Our design approach provides a general strategy for creating binders to protein targets with exposed surface beta edge strands.

PubMed: 33879614
DOI: 10.1073/pnas.2021569118

実験手法

X-RAY DIFFRACTION (2.84 Å)