1aly
From Proteopedia
(New page: 200px<br /> <applet load="1aly" size="450" color="white" frame="true" align="right" spinBox="true" caption="1aly, resolution 2.00Å" /> '''CRYSTAL STRUCTURE O...) |
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| - | [[Image:1aly.gif|left|200px]]<br /> | + | [[Image:1aly.gif|left|200px]]<br /><applet load="1aly" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1aly" size=" | + | |
caption="1aly, resolution 2.00Å" /> | caption="1aly, resolution 2.00Å" /> | ||
'''CRYSTAL STRUCTURE OF HUMAN CD40 LIGAND'''<br /> | '''CRYSTAL STRUCTURE OF HUMAN CD40 LIGAND'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: The CD40 ligand (CD40L) is a member of the tumor necrosis | + | 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== | ==Disease== | ||
| - | Known diseases associated with this structure: Immunodeficiency, X-linked, with hyper-IgM OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300386 300386]], Transposition of the great arteries, dextro-looped OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=608771 608771]] | + | Known diseases associated with this structure: Immunodeficiency, X-linked, with hyper-IgM OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300386 300386]], Transposition of the great arteries, dextro-looped 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=608771 608771]] |
==About this Structure== | ==About this Structure== | ||
| - | 1ALY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1ALY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ALY OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Hsu, Y | + | [[Category: Hsu, Y M.]] |
[[Category: Karpusas, M.]] | [[Category: Karpusas, M.]] | ||
[[Category: Thomas, D.]] | [[Category: Thomas, D.]] | ||
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[[Category: tnf]] | [[Category: tnf]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:45:55 2008'' |
Revision as of 09:45, 21 February 2008
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CRYSTAL STRUCTURE OF HUMAN CD40 LIGAND
Contents |
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 1 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
Page seeded by OCA on Thu Feb 21 11:45:55 2008
Categories: Homo sapiens | Single protein | Hsu, Y M. | Karpusas, M. | Thomas, D. | Cd40 ligand | Cd40l | Cytokine | Hyper-igm syndrome | Tnf
