Crystal structure of extracellular human BAFF, a TNF family member that stimulates B lymphocytes
Crystal structure of extracellular human BAFF, a TNF family member that stimulates B lymphocytes
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DOI：
10.1006/jmbi.2001.5296
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发表时间：
2002-02-01
影响因子：
5.6
通讯作者：
Kalled, SL
中科院分区：
文献类型：
--
作者：
Karpusas, M;Cachero, TG;Kalled, SL
B细胞活化因子（BAFF）是一种属于肿瘤坏死因子（TNF）家族的配体，在调节外周B细胞群的存活和活化中起关键作用，并与自身免疫性疾病有关。已知BAFF与BCMA、TACI和BAFF- r三种受体相互作用，这三种受体与TNF家族的其他受体具有遥远的相似性。我们在2.8埃的分辨率下确定了BAFF的tnf -同源结构域的晶体结构。与其他TNF家族成员相比，该结构显示出显着差异，包括异常长的D-E环，该环参与在假定的受体结合位点形成深凹且带负电荷的区域。BAFF结构进一步用于生成APRIL的同源模型，APRIL是一种密切相关的TNF家族配体，也与BCMA和TACI结合，但不与BAFF- r结合。对BAFF和APRIL推测的受体结合位点的分析表明，D-E环结构和静电表面电位的差异可能是确定BCMA、TACI和BAFF- r结合特异性的重要因素。(C) 2002 Elsevier Science Ltd.
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 Angstrom 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. (C) 2002 Elsevier Science Ltd.