Structure and function of laminin LG modules
Structure and function of laminin LG modules
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DOI：
10.1016/s0945-053x(00)00072-x
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发表时间：
2000-08-01
期刊：
影响因子：
6.9
通讯作者：
Hohenester, E
中科院分区：
文献类型：
--
作者：
Timpl, R;Tisi, D;Hohenester, E
层粘连蛋白G结构域样（LG）模块约180-200个残基被发现在许多细胞外和受体蛋白中，并且通常以串联阵列存在。LG模块涉及与细胞受体（整联蛋白、α-肌营养不良蛋白聚糖）、硫酸化碳水化合物和其他细胞外配体的相互作用。最近确定的层粘连蛋白α 2链的LG模块的晶体结构揭示了一个紧凑的β夹心折叠，并确定了一个新的钙结合位点。肝素、硫苷脂和α-肌营养不良蛋白聚糖的结合表位已通过定点诱变绘制，并显示出相当大的重叠。这些表位位于钙位点周围的表面环中，在其他蛋白质（聚集蛋白、神经毒素）中，这些表位通过选择性剪接进行修饰。有效的配体结合通常需要LG模块串联存在。LG模块中N-和C-末端的紧密接近，以及层粘连蛋白LG 3和LG 4之间的独特连接区域，对LG串联的排列施加了某些限制。可以通过层粘连蛋白G结构域的蛋白水解加工引入进一步的修饰，已知其发生在α 2、α 3和α 4链中。(C)2000 Elsevier Science B.V./国际矩阵生物学学会。All rights reserved.
Laminin G domain-like (LG) modules of approximately 180-200 residues are found in a number of extracellular and receptor proteins and often are present in tandem arrays. LG modules are implicated in interactions with cellular receptors (integrins, alpha-dystroglycan), sulfated carbohydrates and other extracellular ligands. The recently determined crystal structures of LG modules of the laminin alpha 2 chain reveal a compact beta sandwich fold and identify a novel calcium binding site. Binding epitopes for heparin, sulfatides and alpha-dystroglycan have been mapped by site-directed mutagenesis and show considerable overlap. The epitopes are located in surface loops around the calcium site, which in other proteins (agrin, neurexins) are modified by alternative splicing. Efficient ligand binding often requires LG modules to be present in tandem. The close proximity of the N- and C-termini in the LG module, as well as a unique link region between laminin LG3 and LG4, impose certain constraints on the arrangement of LG tandems. Further modifications may be introduced by proteolytic processing of laminin G domains, which is known to occur in the alpha 2, alpha 3 and alpha 4 chains. (C) 2000 Elsevier Science B.V./International Society of Matrix Biology. All rights reserved.