TOPOLOGY OF CELL-ADHESION MOLECULES
TOPOLOGY OF CELL-ADHESION MOLECULES
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DOI：
10.1073/pnas.86.3.1088
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发表时间：
1989-02-01
影响因子：
11.1
通讯作者：
EDELMAN, GM
中科院分区：
文献类型：
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作者：
BECKER, JW;ERICKSON, HP;EDELMAN, GM
神经细胞粘附分子（N-CAM）以两种主要形式存在[ld（大细胞质结构域）肽和sd（小细胞质结构域）肽]，包含跨膜片段和不同的细胞质结构域，以及第三种形式[ssd（小表面结构域）肽]，缺乏跨膜和细胞质区域。所有形式都具有超过 600 个氨基酸残基的相同胞外区域，该区域也存在于可通过蛋白水解从细胞中释放的片段 (Fr2) 中。肝脏细胞粘附分子 (L-CAM) 表达为与 N-CAM 不同的单一物种，但其细胞外区域也可以作为蛋白水解片段 (Ft1) 获得。通过旋转阴影分子的电子显微镜对 N-CAM 和 L-CAM 的 Ft1 片段的各种形式的估计表明，它们都具有棒状结构，其中包含明显柔性的铰链区。 SSD 链和 N-CAM 的 Fr2 片段都是弯曲成大约 18 和 10 nm 长的臂的单杆。 ld 和 sd 链是较长的弯曲杆，形成包含 2 至 6 个分支的莲座丛；洗涤剂处理将这些玫瑰花结破坏成单杆。阻断同性 N-CAM 结合的特异性抗体标记了 Id/sd 玫瑰花结分支的远端以及 ssd 链和 Fr2 片段的长臂末端。与 N-CAM 富含唾液酸区域结合的抗体在铰链附近结合。这些数据表明N-CAM玫瑰花结是通过其跨膜或细胞质结构域之间的相互作用形成的，而不是通过涉及其同源结合位点的相互作用形成的。 L-CAM Ft1 碎片也是一根弯曲的杆，带有明显灵活的铰链；与SSD链和N-CAM的Fr2片段一样，它不形成聚集体。尽管 L-CAM 和 N-CAM 的氨基酸序列不同，但它们之间的相似性表明它们的一般构型和柔性铰链的存在是确保有效和特异性细胞间粘附的重要因素。
The neural cell adhesion molecule (N-CAM) exists in two major forms [ld (large cytoplasmic domain) peptide and sd (small cytoplasmic domain) peptide] that contain transmembrane segments and different cytoplasmic domains and in a third form [ssd (small surface domain) peptide] that lacks transmembrane and cytoplasmic regions. All forms have the same extracellular region of more than 600 amino acid residues, a region also found in a fragment (Fr2) that can be released from cells by proteolysis. Thel iver cell adhesion moelcule (L-CAM) is expressed as a single species that is distinct from N-CAM, but its extracellular region can also be obtained as a proteolytic fragment (Ft1). Estimation of the various forms of N-CAM and the Ft1 fragment of L-CAM by electron microscopy of rotary shadowed molecules indicated that they all have rod-shaped structures that contain a hinge region which is apparently flexible. Both the ssd chain and the Fr2 fragment of N-CAM are single rods bent into arms approximately 18 and 10 nm long. The ld and sd chains are longer bent rods that form rosettes comprising two to six branches; detergent treatment disrupts these rosettes into single rods. Specific antibodies that block homophilic N-CAM binding labeled the distal ends of the branches of the Id/sd rosettes and the ends of the longer arm of both the ssd chain and the Fr2 fragment. Antibodies that bind to the sialic acid-rich region of N-CAM bound near the hinge. These data indicate that the N-CAM rosetts are formed by interaction between their transmembrane or cytoplasmic domains and not by interactions involving their homophilic binding sites. The L-CAM Ft1 fragment is also a bent rod with an apparently flexible hinger; like the ssd chain and the Fr2 fragment of N-CAM, it does not form aggregates. The similarities between L-CAM and N-CAM, despite their differences in amino acid sequence, suggest that their general configuration and the presence of a flexible hinge are important elements in assuring effective and specific cell-cell adhesion.