Structural Basis of Chemokine Sequestration by CrmD, a Poxvirus-Encoded Tumor Necrosis Factor Receptor
2011

Understanding How a Poxvirus Protein Binds to Chemokines

publication 10 minutes Evidence: high

Author Information

Author(s): Xue Xiaoguang, Lu Qingyu, Wei Hui, Wang Dongli, Chen Dongwei, He Guangjun, Huang Li, Wang Hanzhong, Wang Xinquan

Primary Institution: Tsinghua University, Beijing, People's Republic of China

Hypothesis

The SECRET domain of the poxvirus-encoded tumor necrosis factor receptor CrmD binds to chemokines to inhibit their activity.

Conclusion

The study reveals the structural basis for how the SECRET domain inhibits chemokine activities by interfering with their interactions with receptors and glycosaminoglycans.

Supporting Evidence

  • The SECRET domain binds to chemokines in a manner that inhibits their activity.
  • Mutations in the SECRET domain affect its binding to various chemokines.
  • The study provides crystal structures that illustrate the interaction between the SECRET domain and CX3CL1.
  • Heparin was shown to inhibit the binding of CX3CL1 by the SECRET domain.
  • The SECRET domain can interfere with cell migration induced by chemokines.

Takeaway

This study shows how a virus can use a special protein to grab onto immune signals called chemokines, making it harder for the immune system to fight the virus.

Methodology

The researchers used X-ray crystallography to determine the structure of the SECRET domain and its complex with the chemokine CX3CL1.

Limitations

The study primarily focuses on the interaction between the SECRET domain and a specific chemokine, which may not represent all interactions with other chemokines.

Digital Object Identifier (DOI)

10.1371/journal.ppat.1002162

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