1kd7

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==Overview==
==Overview==
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B cell activating factor (BAFF), a ligand belonging to the tumor necrosis, factor (TNF) family, plays a critical role in regulating survival and, activation of peripheral B cell populations and has been associated with, autoimmune disease. BAFF is known to interact with three receptors, BCMA, TACI and BAFF-R, that have distant similarities with other receptors of, the TNF family. We have determined the crystal structure of the, TNF-homologous domain of BAFF at 2.8 A resolution. The structure reveals, significant differences when compared to other TNF family members, including an unusually long D-E loop that participates in the formation of, a deep, concave and negatively charged region in the putative receptor, binding site. The BAFF structure was further used to generate a homology, model of APRIL, a closely related TNF family ligand that also binds to, BCMA and TACI, but not BAFF-R. Analysis of the putative receptor binding, sites of BAFF and APRIL suggests that differences in the D-E loop, structure and electrostatic surface potentials may be important for, determining binding specificities for BCMA, TACI and BAFF-R.
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B cell activating factor (BAFF), a ligand belonging to the tumor necrosis factor (TNF) family, plays a critical role in regulating survival and activation of peripheral B cell populations and has been associated with autoimmune disease. BAFF is known to interact with three receptors, BCMA, TACI and BAFF-R, that have distant similarities with other receptors of the TNF family. We have determined the crystal structure of the TNF-homologous domain of BAFF at 2.8 A resolution. The structure reveals significant differences when compared to other TNF family members, including an unusually long D-E loop that participates in the formation of a deep, concave and negatively charged region in the putative receptor binding site. The BAFF structure was further used to generate a homology model of APRIL, a closely related TNF family ligand that also binds to BCMA and TACI, but not BAFF-R. Analysis of the putative receptor binding sites of BAFF and APRIL suggests that differences in the D-E loop structure and electrostatic surface potentials may be important for determining binding specificities for BCMA, TACI and BAFF-R.
==About this Structure==
==About this Structure==
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[[Category: Single protein]]
[[Category: Single protein]]
[[Category: Boriack-Sjodin, A.]]
[[Category: Boriack-Sjodin, A.]]
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[[Category: Cachero, T.G.]]
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[[Category: Cachero, T G.]]
[[Category: Hsu, Y-M.]]
[[Category: Hsu, Y-M.]]
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[[Category: Kalled, S.L.]]
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[[Category: Kalled, S L.]]
[[Category: Karpusas, M.]]
[[Category: Karpusas, M.]]
[[Category: Mullen, C.]]
[[Category: Mullen, C.]]
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[[Category: tnf]]
[[Category: tnf]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:12:42 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:32:48 2008''

Revision as of 11:32, 21 February 2008


1kd7, resolution 2.80Å

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Crystal structure of an extracellular domain fragment of human BAFF

Overview

B cell activating factor (BAFF), a ligand belonging to the tumor necrosis factor (TNF) family, plays a critical role in regulating survival and activation of peripheral B cell populations and has been associated with autoimmune disease. BAFF is known to interact with three receptors, BCMA, TACI and BAFF-R, that have distant similarities with other receptors of the TNF family. We have determined the crystal structure of the TNF-homologous domain of BAFF at 2.8 A resolution. The structure reveals significant differences when compared to other TNF family members, including an unusually long D-E loop that participates in the formation of a deep, concave and negatively charged region in the putative receptor binding site. The BAFF structure was further used to generate a homology model of APRIL, a closely related TNF family ligand that also binds to BCMA and TACI, but not BAFF-R. Analysis of the putative receptor binding sites of BAFF and APRIL suggests that differences in the D-E loop structure and electrostatic surface potentials may be important for determining binding specificities for BCMA, TACI and BAFF-R.

About this Structure

1KD7 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Crystal structure of extracellular human BAFF, a TNF family member that stimulates B lymphocytes., Karpusas M, Cachero TG, Qian F, Boriack-Sjodin A, Mullen C, Strauch K, Hsu YM, Kalled SL, J Mol Biol. 2002 Feb 1;315(5):1145-54. PMID:11827482

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