A 3-D MODEL FOR THE CD40 LIGAND PREDICTS THAT IT IS A COMPACT TRIMER SIMILAR TO THE TUMOR NECROSIS FACTORS

Based on the similarity in primary structure between the newly characterized ligand for CD40 (CD40L) and the tumor necrosis factors (TNFs), we have modeled a detailed 3-D structure for CD40L. We used the known structure of TNFalpha as a template for the generation of the CD40L model. The soundness of the model-building algorithms was verified by constructing a 3-D model of TNFbeta and comparing it to its crystallographically determined structure. The CD40L sequence is entirely compatible with the 'jelly-roll' beta-strand structure characteristic of the TNFs. Like the TNFs, CD40L is predicted to form a compact trimer, although the interactions between monomers are distinct from those found in the TNFs. The model predicts which regions of CD40L could interact with its receptor(s) and which amino acids are essential for the maintenance of its trimeric structure.