Structural correlations in the family of small leucine-rich repeat proteins and proteoglycans
Structural correlations in the family of small leucine-rich repeat proteins and proteoglycans
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DOI：
10.1016/j.jsb.2006.01.016
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发表时间：
2006-08-01
影响因子：
3
通讯作者：
Bella, Jordi
中科院分区：
文献类型：
--
作者：
McEwan, Paul A.;Scott, Paul G.;Bella, Jordi
富含亮氨酸的小重复序列蛋白和蛋白聚糖（slrp）家族包含几个细胞外基质分子，这些分子在结构上由富含亮氨酸的重复序列（lrr）组成的蛋白质核心相连，两侧是两个保守的富含半胱氨酸的区域。小蛋白聚糖装饰素是典型的SLRP。Decorin存在于多种结缔组织中，通常“装饰”胶原原纤维，并参与重要的生物学功能，包括纤维性胶原的组装调节和细胞粘附调节。已知有几种slrp调节胶原纤维形成，有证据表明它们可能具有其他生物学功能。我们最近确定了decorin蛋白核心的晶体结构，这是SLRP家族成员的第一次这样的确定。该结构突出了几个相关性：(1)slrp具有相似的内部重复结构；(2) SLRP分子的弯曲度远低于基于核糖核酸酶抑制剂三维结构的decorin早期模型；(3) n端和c端富含半胱氨酸的区域是保守的盖上基序。此外，该结构表明，decorin通过其LRR结构域的凹表面进行二聚化，这与先前与胶原蛋白的相互作用有关。我们已经确定了装饰素和光学蛋白（另一种SLRP）在溶液中形成稳定的二聚体。修饰素二聚化过程中残基的守恒表明其他slrp的二聚化模式是相似的。综上所述，这些结果表明需要重新评估目前接受的SLRP与其配体相互作用的模型。(c) 2006年Elsevier Inc.出版
The family of small leucine-rich repeat proteins and proteoglycans (SLRPs) contains several extracellular matrix molecules that are structurally related by a protein core composed of leucine-rich repeats (LRRs) flanked by two conserved cysteine-rich regions. The small proteoglycan decorin is the archetypal SLRP. Decorin is present in a variety of connective tissues, typically "decorating" collagen fibrils, and is involved in important biological functions, including the regulation of the assembly of fibrillar collagens and modulation of cell adhesion. Several SLRPs are known to regulate collagen fibrillogenesis and there is evidence that they may share other biological functions. We have recently determined the crystal structure of the protein core of decorin, the first such determination of a member of the SLRP family. This structure has highlighted several correlations: (1) SLRPs have similar internal repeat structures; (2) SLRP molecules are far less curved than an early model of decorin based on the three-dimensional structure of ribonuclease inhibitor; (3) the N-terminal and C-terminal cysteine-rich regions are conserved capping motifs. Furthermore, the structure shows that decorin dimerizes through the concave surface of its LRR domain, which has been implicated previously in its interaction with collagen. We have established that both decorin and opticin, another SLRP, form stable dimers in solution. Conservation of residues involved in decorin dimerization suggests that the mode of dimerization for other SLRPs will be similar. Taken together these results suggest the need for reevaluation of currently accepted models of SLRP interaction with their ligands. (c) 2006 Published by Elsevier Inc.