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Crystal structure of the BAFF–BAFF-R complex and its implications for receptor activation

Nature Structural Biology volume 10, pages 342348 (2003) | Download Citation

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Abstract

B-cell activating factor (BAFF) is a key regulator of B-lymphocyte development. Its biological role is mediated by the specific receptors BCMA, TACI and BAFF-R. We have determined the crystal structure of the extracellular domain of BAFF-R bound to BAFF at a resolution of 3.3 Å. The cysteine-rich domain (CRD) of the BAFF-R extracellular domain adopts a β-hairpin structure and binds to the virus-like BAFF cage in a 1:1 molar ratio. The conserved DxL motif of BAFF-R is located on the tip of the β-turn and is indispensable in the binding of BAFF. The crystal structure shows that a unique dimeric contact occurs between the BAFF-R monomers in the virus-like cage complex. The extracellular domain of TACI contains two CRDs, both of which contain the DxL motif. Modeling of TACI–BAFF complex suggests that both CDRs simultaneously interact with the BAFF dimer in the virus-like cage.

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Acknowledgements

We thank the staff of the Cornell High Energy Synchrotron Source (MacCHESS) and Spring-8 for help with data collection. This work was supported in part by the Molecular Medicine Research Group Program of the Ministry of Science (J.-O.L) and Technology and by a Korea Research Foundation Grant (H.L.).

Author information

Affiliations

  1. Department of Biological Science, Korea Advanced Institute of Science and Technology, Daejeon, Korea.

    • Ho Min Kim
    •  & Ook Joon Yoo
  2. Department of Biology, Chungnam National University, Daejeon, Korea.

    • Kyung Sook Yu
    •  & Sang-Gi Paik
  3. Department of Chemistry and School of Molecular Science (BK21), Korea Advanced Institute of Science and Technology, Daejeon, Korea.

    • Mi Eun Lee
    • , Dong Ryeol Shin
    •  & Jie-Oh Lee
  4. Department of Biochemistry, Chungnam National University, Daejeon, Korea.

    • Young Sang Kim
  5. Institute of Biotechnology, Chungnam National University, Daejeon, Korea.

    • Young Sang Kim
    • , Sang-Gi Paik
    •  & Hayyoung Lee
  6. BioMedical Research Center, Korea Advanced Institute of Science and Technology, Daejeon, Korea.

    • Ook Joon Yoo

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The authors declare no competing financial interests.

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Correspondence to Hayyoung Lee or Jie-Oh Lee.

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https://doi.org/10.1038/nsb925

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