7DA4

Cryo-EM structure of amyloid fibril formed by human RIPK3

Summary for 7DA4

• Entry DOI: 10.2210/pdb7da4/pdb
• EMDB information: 30622
• Descriptor: Receptor-interacting serine/threonine-protein kinase 3 (1 entity in total)
• Functional Keywords: amyloid fibril, protein fibril
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 3
• Total formula weight: 45935.26

Authors

Zhao, K.,Ma, Y.Y.,Sun, Y.P.,Li, D.,Liu, C. (deposition date: 2020-10-14, release date: 2021-04-28, Last modification date: 2024-03-27)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (4.24 Å)