Solution structure of the transforming growth factor beta-binding protein-like module, a domain associated with matrix fibrils
Solution structure of the transforming growth factor beta-binding protein-like module, a domain associated with matrix fibrils
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DOI：
10.1093/emboj/16.22.6659
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发表时间：
1997-11-17
期刊：
影响因子：
11.4
通讯作者：
Handford, PA
中科院分区：
文献类型：
--
作者：
Yuan, XM;Downing, AK;Handford, PA
在这里，我们描述了转化生长因子β (tgf - β)结合蛋白样（TB）结构域的高分辨率核磁共振（NMR）结构，该结构域来自马凡氏综合征（MFS）中有缺陷的蛋白人纤原蛋白-1。该结构域存在于纤维蛋白和潜伏的tgf - β结合蛋白（ltbp）中，这些蛋白位于细胞外基质的纤维结构中。TB结构域表现出一种新的褶皱，它是球形的，由六条反平行的β链和两条α螺旋组成。在TB结构域序列中保守的不寻常的半胱氨酸三重态定位于疏水核心，位于α -螺旋的c端。该结构由四个以1- 3,2 - 6,4 - 7,5 -8模式配对的二硫键稳定，其中两个是溶剂暴露的。对mfs引起的突变和纤原蛋白-1细胞结合RGD位点的分析为TB结构域相互作用的表面特异性提供了第一个线索。对LTBP-1同源TB结构域（残基1018-1080）的建模表明疏水接触可能在其与tgf - β 1潜伏期相关肽的相互作用中起作用。
Here we describe the high resolution nuclear magnetic resonance (NMR) structure of a transforming growth factor beta (TGF-beta)-binding protein-like (TB) domain, which comes from human fibrillin-1, the protein defective in the Marfan syndrome (MFS). This domain is found in fibrillins and latent TGF-beta-binding proteins (LTBPs) which are localized to fibrillar structures in the extracellular matrix, The TB domain manifests a novel fold which is globular and comprises six antiparallel beta-strands and two alpha-helices. An unusual cysteine triplet conserved in the sequences of TB domains is localized to the hydrophobic core, at the C-terminus of an alpha-helix. The structure is stabilized by four disulfide bonds which pair in a 1-3, 2-6, 4-7, 5-8 pattern, two of which are solvent exposed, Analyses of MFS-causing mutations and the fibrillin-1 cell-binding RGD site provide the first clues to the surface specificity of TB domain interactions, Modelling of a homologous TB domain from LTBP-1 (residues 1018-1080) suggests that hydrophobic contacts may play a role in its interaction with the TGF-beta 1 latency-associated peptide.