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TitleThe structure of a minimum amyloid fibril core formed by necroptosis-mediating RHIM of human RIPK3.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 118, Issue 14, Year 2021
Publish dateApr 6, 2021
AuthorsXialian Wu / Yeyang Ma / Kun Zhao / Jing Zhang / Yunpeng Sun / Yichen Li / Xingqi Dong / Hong Hu / Jing Liu / Jian Wang / Xia Zhang / Bing Li / Huayi Wang / Dan Li / Bo Sun / Junxia Lu / Cong Liu /
PubMed AbstractReceptor-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 ...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.
External linksProc Natl Acad Sci U S A / PubMed:33790016 / PubMed Central
MethodsEM (helical sym.) / NMR (solid-state)
Resolution4.24 Å
Structure data

30622

7da4

EMDB-30622, PDB-7da4:
Cryo-EM structure of amyloid fibril formed by human RIPK3
Method: EM (helical sym.) / Resolution: 4.24 Å

PDB-7dac:
Human RIPK3 amyloid fibril revealed by solid-state NMR
Method: SOLID-STATE NMR

Source
  • homo sapiens (human)
KeywordsPROTEIN FIBRIL / Amyloid fibril / programmed necrosis / amyloid

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