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Article
Nature Structural Biology  10, 342 - 348 (2003)
Published online: 25 April 2003; | doi:10.1038/nsb925

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

Ho Min Kim1, Kyung Sook Yu2, Mi Eun Lee3, Dong Ryeol Shin3, Young Sang Kim4, 5, Sang-Gi Paik2, 5, Ook Joon Yoo1, 6, Hayyoung Lee5 & Jie-Oh Lee3

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

2  Department of Biology, Chungnam National University, Daejeon, Korea.

3  Department of Chemistry and School of Molecular Science (BK21), Korea Advanced Institute of Science and Technology, Daejeon, Korea.

4  Department of Biochemistry, Chungnam National University, Daejeon, Korea.

5  Institute of Biotechnology, Chungnam National University, Daejeon, Korea.

6  BioMedical Research Center, Korea Advanced Institute of Science and Technology, Daejeon, Korea.

Correspondence should be addressed to Hayyoung Lee hlee@cnu.ac.kr or Jie-Oh Lee jieoh@kaist.ac.kr
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 beta-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 beta-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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Nature Structural & Molecular Biology
ISSN: 1545-9993
EISSN: 1545-9985
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