7DAC

Human RIPK3 amyloid fibril revealed by solid-state NMR

7DAC の概要

• エントリーDOI: 10.2210/pdb7dac/pdb
• NMR情報: BMRB: 36392
• 分子名称: Receptor-interacting serine/threonine-protein kinase 3 (1 entity in total)
• 機能のキーワード: programmed necrosis, amyloid, protein fibril
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 59315.36

構造登録者

Wu, X.L.,Zhang, J.,Dong, X.Q.,Liu, J.,Li, B.,Hu, H.,Wang, J.,Wang, H.Y.,Lu, J.X. (登録日: 2020-10-16, 公開日: 2021-04-28, 最終更新日: 2024-05-01)

主引用文献

Wu, X.,Ma, Y.,Zhao, K.,Zhang, J.,Sun, Y.,Li, Y.,Dong, X.,Hu, H.,Liu, J.,Wang, J.,Zhang, X.,Li, B.,Wang, H.,Li, D.,Sun, B.,Lu, J.,Liu, C.
The structure of a minimum amyloid fibril core formed by necroptosis-mediating RHIM of human RIPK3.
Proc.Natl.Acad.Sci.USA, 118:-, 2021

PubMed Abstract: Receptor-interacting protein kinases 3 (RIPK3), a central node in necroptosis, polymerizes in response to the upstream signals and then activates its downstream mediator to induce cell death. The active polymeric form of RIPK3 has been indicated as the form of amyloid fibrils assembled via its RIP homotypic interaction motif (RHIM). In this study, we combine cryogenic electron microscopy and solid-state NMR to determine the amyloid fibril structure of RIPK3 RHIM-containing C-terminal domain (CTD). The structure reveals a single protofilament composed of the RHIM domain. RHIM forms three β-strands (referred to as strands 1 through 3) folding into an S shape, a distinct fold from that in complex with RIPK1. The consensus tetrapeptide VQVG of RHIM forms strand 2, which zips up strands 1 and 3 via heterozipper-like interfaces. Notably, the RIPK3-CTD fibril, as a physiological fibril, exhibits distinctive assembly compared with pathological fibrils. It has an exceptionally small fibril core and twists in both handedness with the smallest pitch known so far. These traits may contribute to a favorable spatial arrangement of RIPK3 kinase domain for efficient phosphorylation.

PubMed: 33790016
DOI: 10.1073/pnas.2022933118

実験手法

SOLID-STATE NMR