3QD6

Crystal structure of the CD40 and CD154 (CD40L) complex

Summary for 3QD6

• Entry DOI: 10.2210/pdb3qd6/pdb
• Descriptor: CD40 ligand, Tumor necrosis factor receptor superfamily member 5, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: immune regulator, receptor, cytokine-cytokine receptor complex, cytokine/cytokine receptor
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 10
• Total formula weight: 176015.15

Authors

Lee, J.-O.,Kim, Y.J.,Song, D.H.,Kim, H.M.,Park, B.S. (deposition date: 2011-01-18, release date: 2011-02-02, Last modification date: 2024-10-30)

Primary citation

An, H.-J.,Kim, Y.J.,Song, D.H.,Park, B.S.,Kim, H.M.,Lee, J.D.,Paik, S.-G.,Lee, J.-O.,Lee, H.
Crystallographic and mutational analysis of the CD40-CD154 complex and its implications for receptor activation
J.Biol.Chem., 286:11226-11235, 2011

PubMed 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 Å 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.

PubMed: 21285457
DOI: 10.1074/jbc.M110.208215

Experimental method

X-RAY DIFFRACTION (3.5 Å)