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Updated: May 28, 2026

Atomic Scale Structural Studies of Macromolecular Assemblies by Solid-state Nuclear Magnetic Resonance Spectroscopy
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Atomic Scale Structural Studies of Macromolecular Assemblies by Solid-state Nuclear Magnetic Resonance Spectroscopy

Published on: September 17, 2017

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Structural studies of an antinecroptosis viral:human functional heteroamyloid M45:RIPK3 using SSNMR

Chengming He1, Nikhil R Varghese2,3, Eric G Keeler1

  • 1Department of Chemistry, Columbia University, New York, NY 10027.

Proceedings of the National Academy of Sciences of the United States of America
|April 27, 2026
PubMed

Insights

Viral M45 protein inhibits necroptosis by forming amyloid assemblies with RIPK3. This study reveals the high-resolution structure of the M45:RIPK3 complex, detailing how these viral and host proteins coassemble to block immune signaling.

Area of Science:

  • Immunology
  • Structural Biology
  • Virology

Background:

  • Necroptosis is a crucial innate immune defense mechanism regulated by RIP-homotypic interaction motif (RHIM)-based amyloid assemblies.
  • Viral proteins, like murine cytomegalovirus's M45, can inhibit necroptosis through RHIM-dependent mechanisms.

Purpose of the Study:

  • To elucidate the structural basis of how viral M45 protein forms heteroamyloids with the host kinase RIPK3.
  • To understand the molecular mechanism by which M45:RIPK3 assemblies inhibit necroptosis.

Main Methods:

  • High-resolution structural analysis of the M45:RIPK3 complex.
  • Site-directed mutagenesis to investigate the role of specific residues in M45 during coassembly.

Main Results:

  • The M45:RIPK3 complex forms an alternating amyloid-state structure.
  • Mutagenesis studies identified an extended interface critical for heteromeric fibril formation.
  • Key interactions stabilize these viral:host amyloid fibrils.

Conclusions:

  • The M45:RIPK3 heteroamyloid acts as an antinecroptotic signal by preventing pronecroptotic complex formation and RIPK3 autophosphorylation.
  • This structural insight provides a mechanism for viral evasion of host innate immunity.
Keywords:
RIPK3SSNMRcell deathfunctional amyloidsprotein structure determination

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