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Structural transformation-mediated dimerization of caspase recruitment domain revealed by the crystal structure of

Chang Min Kim1, Hyun Ji Ha1, Sunghark Kwon1

  • 1College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea.

Journal of Structural Biology
|January 10, 2019
PubMed

Insights

Viral caspase recruitment domain (CARD)-only proteins (COPs) inhibit host immunity. We determined the first viral COP structure, revealing a unique dimer formation mechanism that may be a novel strategy in the death domain superfamily.

Area of Science:

  • Structural biology
  • Immunology
  • Virology

Background:

  • Caspase recruitment domain (CARD)-only proteins (COPs) are key regulators of apoptosis, inflammation, and innate immunity.
  • COPs inhibit NOD-like receptor complexes, including the inflammasome and NODosome, which are critical for caspase-1 activation.
  • Viral COPs are employed by viruses to evade host immune responses.

Purpose of the Study:

  • To elucidate the molecular mechanism by which viral COPs inhibit host immunity.
  • To determine the first high-resolution structure of a viral COP.

Main Methods:

  • X-ray crystallography was used to solve the three-dimensional structure of a viral COP.
  • Structural analysis was performed and compared with existing structures of death domain superfamily members.

Main Results:

  • The determined structure revealed that the viral COP forms a unique structural transformation-mediated dimer.
  • This dimerization mechanism has not been previously observed in any CARD domain structural studies.
  • The findings suggest a novel mode of dimer assembly within the broader death domain superfamily.

Conclusions:

  • Structural transformation-mediated dimerization represents a potentially new strategy for protein-protein interactions within the death domain superfamily.
  • Understanding this mechanism provides insights into viral immune evasion strategies and potential therapeutic targets.

Keywords:
ApoptosisCARD-only proteinCaspase recruitment domainCrystal structureDeath domain superfamilyDomain swapping

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