X-ray structure of junctional adhesion molecule: structural basis for homophilic adhesion via a novel dimerization motif
X-ray structure of junctional adhesion molecule: structural basis for homophilic adhesion via a novel dimerization motif
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DOI：
10.1093/emboj/20.16.4391
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发表时间：
2001-08-15
期刊：
影响因子：
11.4
通讯作者：
Hennig, M
中科院分区：
文献类型：
--
作者：
Kostrewa, D;Brockhaus, M;Hennig, M
连接粘附分子（JAM）是一类免疫球蛋白样单跨跨膜分子，在内皮细胞、上皮细胞、白细胞和心肌中表达。 JAM 被认为有助于紧密连接的粘附功能并调节白细胞的迁移。我们以 2.5 埃分辨率描述了小鼠 JAM (rsJAM) 重组胞外部分的晶体结构。 rsJAM 由两个免疫球蛋白样结构域组成，它们通过构象限制的短接头连接。两个 rsJAM 分子形成 U 形二聚体，N 端结构域之间具有高度互补的相互作用。两个盐桥由一个新的二聚化基序 R(V,I,L)E 以互补的方式形成，该基序对于溶液中 rsJAM 二聚体的形成至关重要，并且是 JAM 家族已知成员所共有的。基于晶体堆积和突变体 rsJAM 的研究，我们提出了 JAM 的同质粘附模型。在此模型中，U 形 JAM 二聚体在细胞表面顺式取向，并通过其 N 端结构域与来自相对细胞表面的 JAM 二聚体的反式相互作用形成二维网络。
Junctional adhesion molecules (JAMs) are a family of immunoglobulin-like single-span transmembrane molecules that are expressed in endothelial cells, epithelial cells, leukocytes and myocardia. JAM has been suggested to contribute to the adhesive function of tight junctions and to regulate leukocyte transmigration. We describe the crystal structure of the recombinant extracellular part of mouse JAM (rsJAM) at 2.5 Angstrom resolution. rsJAM consists of two immunoglobulin-like domains that are connected by a conformationally restrained short linker. Two rsJAM molecules form a U-shaped dimer with highly complementary interactions between the N-terminal domains. Two salt bridges are formed in a complementary manner by a novel dimerization motif, R(V,I,L)E, which is essential for the formation of rsJAM dimers in solution and common to the known members of the JAM family. Based on the crystal packing and studies with mutant rsJAM, we propose a model for homophilic adhesion of JAM. In this model, U-shaped JAM dimers are oriented in cis on the cell surface and form a two-dimensional network by transinteractions of their N-terminal domains with JAM dimers from an opposite cell surface.