title: Construction and analysis of a detailed three-dimensional model of the ligand binding domain of the human B cell receptor CD40.
abstract: The interaction between the human B cell receptor CD40 and its ligand on T cells is critical for B cell proliferation and the regulation of humoral immune responses. CD40 is a member of the tumor necrosis factor receptor (TNFR) family. We report here the construction and analysis of a detailed three-dimensional model of the TNFR-homologous extracellular region of CD40. This study provides an example for structure-based model building in the presence of low sequence similarity. The assessment of model quality and sequence-structure compatibility is emphasized, and limitations of the model are discussed. The current CD40 model predicts structural details beyond the backbone level. Features of the CD40 ligand binding site are discussed in conjunction with the results of a previous mutagenesis study.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121, USA.
authors.forename: J
authors.initials: J
authors.lastname: Bajorath
authors.forename: A
authors.initials: A
authors.lastname: Aruffo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D019013:CD40 Antigens / Q000737:chemistry / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D013237:Stereoisomerism; D048008:TNF Receptor-Associated Factor 3; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
chemical_list: D019013:CD40 Antigens; D002352:Carrier Proteins; D008024:Ligands; D018124:Receptors, Tumor Necrosis Factor; D048008:TNF Receptor-Associated Factor 3; C090656:TRAF3 protein, human; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins