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CRYSTAL STRUCTURE OF HUMAN CD40 LIGAND

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

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.

Disease

Known diseases associated with this structure: Immunodeficiency, X-linked, with hyper-IgM OMIM:[300386], Transposition of the great arteries, dextro-looped OMIM:[608771]

About this Structure

1ALY is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

2 A crystal structure of an extracellular fragment of human CD40 ligand., Karpusas M, Hsu YM, Wang JH, Thompson J, Lederman S, Chess L, Thomas D, Structure. 1995 Oct 15;3(10):1031-9. PMID:8589998

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