Homophilic and Heterophilic Interactions of Type II Cadherins Identify Specificity Groups Underlying Cell-Adhesive Behavior.
Homophilic and Heterophilic Interactions of Type II Cadherins Identify Specificity Groups Underlying Cell-Adhesive Behavior.
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DOI：
10.1016/j.celrep.2018.04.012
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发表时间：
2018-05-08
期刊：
影响因子：
8.8
通讯作者：
Shapiro L
中科院分区：
文献类型：
--
作者：
Brasch J;Katsamba PS;Harrison OJ;Ahlsén G;Troyanovsky RB;Indra I;Kaczynska A;Kaeser B;Troyanovsky S;Honig B;Shapiro L
II型钙粘蛋白是细胞-细胞粘附蛋白，对组织图案化和神经元靶向至关重要，但其分子结合密码仍知之甚少。在这里，我们描绘了II型钙粘蛋白细胞粘附区域的结合偏好，揭示了广泛的异嗜性之间的相互作用，除了嗜同性的相互作用。从我们的分析中出现了三个不同的特异性组，其成员具有高度相似的异嗜性结合模式并有利于彼此结合。来自每个特异性组的粘附片段的结构确认了在整个家族中保守的几乎相同的二聚体拓扑结构，允许其保守性对应于特异性偏好的界面残基被识别。我们表明，这些残基的靶向突变转换生物物理和共培养试验中特异性组之间的结合偏好。我们的研究结果提供了一个详细的了解II型钙粘蛋白的相互作用地图和定义其在组织图案化的作用和新兴的重要性，他们的嗜异性相互作用在神经连接的基础。II型钙粘蛋白是主要在CNS中表达的脊椎动物细胞粘附蛋白家族。Brasch等人测量了粘附片段之间的结合，揭示了嗜同性和广泛的选择性嗜异性结合，其特异性定义了相似的钙粘蛋白组。结构揭示共同的粘合剂二聚体，与残基管理细胞粘附特异性。
Type II cadherins are cell-cell adhesion proteins critical for tissue patterning and neuronal targeting but whose molecular binding code remains poorly understood. Here, we delineate binding preferences for type II cadherin cell-adhesive regions, revealing extensive heterophilic interactions between specific pairs, in addition to homophilic interactions. Three distinct specificity groups emerge from our analysis with members that share highly similar heterophilic binding patterns and favor binding to one another. Structures of adhesive fragments from each specificity group confirm near-identical dimer topology conserved throughout the family, allowing interface residues whose conservation corresponds to specificity preferences to be identified. We show that targeted mutation of these residues converts binding preferences between specificity groups in biophysical and co-culture assays. Our results provide a detailed understanding of the type II cadherin interaction map and a basis for defining their role in tissue patterning and for the emerging importance of their heterophilic interactions in neural connectivity. Type II cadherins are a family of vertebrate cell adhesion proteins expressed primarily in the CNS. Brasch et al. measure binding between adhesive fragments, revealing homophilic and extensive selective heterophilic binding with specificities that define groups of similar cadherins. Structures reveal common adhesive dimers, with residues governing cell-adhesive specificity.
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影响因子：
16.2
作者：
Basu, Raunak;Duan, Xin;Williams, Megan E.
通讯作者：
Williams, Megan E.
影响因子：
19
作者：
Brasch J;Harrison OJ;Honig B;Shapiro L
通讯作者：
Shapiro L
影响因子：
3.5
作者：
BURLEY, SK;PETSKO, GA
通讯作者：
PETSKO, GA
影响因子：
5.3
作者：
Fogel, Adam I.;Akins, Michael R.;Biederer, Thomas
通讯作者：
Biederer, Thomas
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH