Crystallographic and mutational analysis of the CD40-CD154 complex and its implications for receptor activation
SCIE
SCOPUS
- Title
- Crystallographic and mutational analysis of the CD40-CD154 complex and its implications for receptor activation
- Authors
- KIM, YOUNGJIN
- Date Issued
- 2011-04-01
- Publisher
- ASBMB
- Abstract
- CD40 is a tumor necrosis factor receptor (TNFR) family protein that plays an important role in B cell development. CD154/CD40L is the physiological ligand of CD40. We have determined the crystal structure of the CD40-CD154 complex at 3.5 angstrom resolution. The binding site of CD40 is located in a crevice formed between two CD154 subunits. Charge complementarity plays a critical role in the CD40-CD154 interaction. Some of the missense mutations found in hereditary hyper-IgM syndrome can be mapped to the CD40-CD154 interface. The CD40 interaction area of one of the CD154 subunits is twice as large as that of the other subunit forming the binding crevice. This is because cysteine-rich domain 3 (CRD3) of CD40 has a disulfide bridge in an unusual position that alters the direction of the ladder-like structure of CD40. The Ser(132) loop of CD154 is not involved in CD40 binding but its substitution significantly reduces p38- and ERK-dependent signaling by CD40, whereas JNK-dependent signaling is not affected. These findings suggest that ligand-induced di- or trimerization is necessary but not sufficient for complete activation of CD40.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/96467
- DOI
- 10.1074/jbc.M110.208215
- ISSN
- 0021-9258
- Article Type
- Article
- Citation
- JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 286, no. 13, page. 11226 - 11235, 2011-04-01
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