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The European CD40L Defect Database

This database was originally developed by the Glaxo (now GSK) group at SIB. It is no longer maintained and has not been updated since 1996. However, the information provided by CD40Lbase continues to be valid. A much more up-to-date database is available.

Structural aspects of CD40L

The ligand: CD40L

CD40L is a member of the tumor necrosis factor (TNF) family of proteins which form homotrimers. Despite their relatively low sequence identity, TNFalpha, TNFbeta(LTalpha) and CD40L share a high degree of structural simlarity and each monomer folds as a beta-sheet sandwich of Greek key topology. The other members of this protein family are expected to adopt a similar three-dimensional structure.

Sequence information:

  1. A few pairwise identity levels.
  2. A multiple seqeunce alignment.

Structure information:

  1. The Brookhaven Data Bank entries for:

  2. SWISS-3DIMAGEs for:

The Receptor: CD40

CD40 is a transmembrane glycoprotein expressed by B lymphocytes, but also detected on other cell types or tumors, particularly carcinomas. As for CD40L, CD40 is part of a large protein family, the TNF-receptor family. The CD40L trimer is expected to bind three CD40 molecules, very much in the same way the TNFbeta trimer binds three TNF-55R receptors.

A few references:


Reference 1:

RA   M. C. Peitsch & C. V. Jongeneel.
RT   "A 3-dimensional model for the cd40 ligand predicts that it is a compact 
RT    trimer similar to the tumor necrosis factors"
RL   INT IMMUNOL 5:233-238 (1993) 
	MEDLINE: 93200072.

Reference 2:

RA   J. Bajorath, R. Stenkamp & A. Aruffo.
RT   "Knowledge-based model building of proteins: concepts and examples."
RL   Protein Sci 2:1798-1810(1993)
	MEDLINE: 94093388.

Reference 3:

RA   Karpsusas M., Hsu Y.-M., Wang J.-H., Thompson J., Lederman S.,
RA   CHESS L., THOMAS D.;
RT   "2A crystal structure of an extracellular fragment of human CD40 ligand."
RL   STRUCTURE 3:1031-1039(1995).

Reference 4:

RA   M. C. Peitsch & J. Tschopp.
RT   "Comparative molecular modelling of the Fas-ligand andother members of 
RT    the TNF family."
RL   MOL IMMUNOL 32:761-772 (1995) 
	MEDLINE: 95388076.

Reference 5:

RA   M. Hahne, M. C. Peitsch, M. Irmler, M. Schroter, B. Lowin, M. Rousseau, 
RA   C. Bron, T. Renno, L. French & J. Tschopp.
RT   "Characterization of the non-functional Fas ligand of gldmice."
RL   INT IMMUNOL 7:1381-1386(1995) 
	MEDLINE: 96091792.

Reference 6:

RA   J. Bajorath, J. S. Marken, N. J. Chalupny, T. L. Spoon, A. W. Siadak, 
RA   M. Gordon, R. J. Noelle, D.Hollenbaugh & A. Aruffo.
RT   "Analysis of gp39/CD40 interactions using molecular models and
RT    site-directed mutagenesis."
RL   Biochemistry 34:9884-9892(1995)
	MEDLINE: 95002262.
Last modified 13/Jun/2001 by ELG