1aly: Difference between revisions

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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="~~450~~" color="white" frame="true" align="right" spinBox="true"

caption="1aly, resolution 2.00Å" />

'''CRYSTAL STRUCTURE OF HUMAN CD40 LIGAND'''<br />

==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.

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:[[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==

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://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1ALY OCA].

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==

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[[Category: Homo sapiens]]

[[Category: Single protein]]

[[Category: Hsu, Y.M.]]

[[Category: Hsu, Y M.]]

[[Category: Karpusas, M.]]

[[Category: Thomas, D.]]

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[[Category: tnf]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Mon Nov 12 15~~:59:~~41 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:45:55 2008''

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@@ Line 1: / Line 1: @@
-[[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="450" color="white" frame="true" align="right" spinBox="true"
 caption="1aly, resolution 2.00&Aring;" />
 '''CRYSTAL STRUCTURE OF HUMAN CD40 LIGAND'''<br />
 ==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.
+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:[[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==
-ALY 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1ALY OCA].
+ALY 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==
@@ Line 17: / Line 16: @@
 [[Category: Homo sapiens]]
 [[Category: Single protein]]
-[[Category: Hsu, Y.M.]]
+[[Category: Hsu, Y M.]]
 [[Category: Karpusas, M.]]
 [[Category: Thomas, D.]]
@@ Line 26: / Line 25: @@
 [[Category: tnf]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 15:59:41 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:45:55 2008''