Crystal structure of the nonclassical cadherin‐17 N‐terminus and implications for its adhesive binding mechanism,Acta Crystallographica Section F

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Crystal structure of the nonclassical cadherin‐17 N‐terminus and implications for its adhesive binding mechanism
Acta Crystallographica Section F ( IF 1.1 ) Pub Date : 2021-03-08 , DOI: 10.1107/s2053230x21002247
Michelle E Gray ₁ , Marcos Sotomayor ₁

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The cadherin superfamily of calcium‐dependent cell‐adhesion proteins has over 100 members in the human genome. All members of the superfamily feature at least a pair of extracellular cadherin (EC) repeats with calcium‐binding sites in the EC linker region. The EC repeats across family members form distinct complexes that mediate cellular adhesion. For instance, classical cadherins (five EC repeats) strand‐swap their N‐termini and exchange tryptophan residues in EC1, while the clustered protocadherins (six EC repeats) use an extended antiparallel `forearm handshake' involving repeats EC1–EC4. The 7D‐cadherins, cadherin‐16 (CDH16) and cadherin‐17 (CDH17), are the most similar to classical cadherins and have seven EC repeats, two of which are likely to have arisen from gene duplication of EC1–2 from a classical ancestor. However, CDH16 and CDH17 lack the EC1 tryptophan residue used by classical cadherins to mediate adhesion. The structure of human CDH17 EC1–2 presented here reveals features that are not seen in classical cadherins and that are incompatible with the EC1 strand‐swap mechanism for adhesion. Analyses of crystal contacts, predicted glycosylation and disease‐related mutations are presented along with sequence alignments suggesting that the novel features in the CDH17 EC1–2 structure are well conserved. These results hint at distinct adhesive properties for 7D‐cadherins.

中文翻译：

非经典钙粘蛋白-17 N 末端的晶体结构及其对其粘合机制的影响

钙依赖性细胞粘附蛋白的钙粘蛋白超家族在人类基因组中有 100 多个成员。该超家族的所有成员都至少具有一对细胞外钙粘蛋白 (EC) 重复序列，EC 接头区域具有钙结合位点。 EC 在家族成员之间重复形成介导细胞粘附的独特复合物。例如，经典钙粘蛋白（五个 EC 重复序列）链交换其 N 末端并交换 EC1 中的色氨酸残基，而簇状原钙粘蛋白（六个 EC 重复序列）使用涉及重复 EC1-EC4 的扩展反平行“前臂握手”。 7D-钙粘蛋白、钙粘蛋白-16 (CDH16) 和钙粘蛋白-17 (CDH17) 与经典钙粘蛋白最相似，并且有 7 个 EC 重复，其中两个可能是由经典钙粘蛋白 EC1-2 的基因重复引起的。祖先。然而，CDH16 和 CDH17 缺乏经典钙粘蛋白用来介导粘附的 EC1 色氨酸残基。这里介绍的人 CDH17 EC1-2 的结构揭示了经典钙粘蛋白中未见的特征，并且与 EC1 链交换粘附机制不相容。对晶体接触、预测的糖基化和疾病相关突变的分析以及序列比对表明 CDH17 EC1-2 结构中的新特征得到了很好的保守。这些结果暗示了 7D-钙粘蛋白的独特粘附特性。

更新日期：2021-03-08

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