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| '''CRYSTAL STRUCTURE OF HUMAN CD40 LIGAND'''
| | ===CRYSTAL STRUCTURE OF HUMAN CD40 LIGAND=== |
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| ==Overview==
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| BACKGROUND: The CD40 ligand (CD40L) is a member of the tumor necrosis factor (TNF) family of proteins and is transiently expressed on the surface of activated T cells. The binding of CD40L to CD40, which is expressed on the surface of B cells, provides a critical and unique pathway of cellular activation resulting in antibody isotype switching, regulation of apoptosis, and B cell proliferation and differentiation. Naturally occurring mutations of CD40L result in the clinical hyper-IgM syndrome, characterized by an inability to produce immunoglobulins of the IgG, IgA and IgE isotypes. RESULTS: We have determined the crystal structure of a soluble extracellular fragment of human CD40L to 2 A resolution and with an R factor of 21.8%. Although the molecule forms a trimer similar to that found for other members of the TNF family, such as TNF alpha and lymphotoxin-alpha, and exhibits a similar overall fold, there are considerable differences in several loops including those predicted to be involved in CD40 binding. CONCLUSIONS: The structure suggests that most of the hyper-IgM syndrome mutations affect the folding and stability of the molecule rather than the CD40-binding site directly. Despite the fact that the hyper-IgM syndrome mutations are dispersed in the primary sequence, a large fraction of them are clustered in space in the vicinity of a surface loop, close to the predicted CD40-binding site.
| | The line below this paragraph, {{ABSTRACT_PUBMED_8589998}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 8589998 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_8589998}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Hyper-igm syndrome]] | | [[Category: Hyper-igm syndrome]] |
| [[Category: Tnf]] | | [[Category: Tnf]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 10:26:03 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 17:07:29 2008'' |
