Structural basis of adhesive binding by desmocollins and desmogleins
Structural basis of adhesive binding by desmocollins and desmogleins
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DOI：
10.1073/pnas.1606272113
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发表时间：
2016-06-28
影响因子：
11.1
通讯作者：
Shapiro, Lawrence
中科院分区：
文献类型：
--
作者：
Harrison, Oliver J.;Brasch, Julia;Shapiro, Lawrence
桥粒是细胞间的粘附连接，赋予脊椎动物组织强度。它们密集有序的细胞间附着是由桥粒芯蛋白（Dsgs）和桥粒柯林斯（Dscs）形成的，但这些专门的钙粘蛋白之间的跨细胞相互作用的性质尚不清楚。在这里，使用溶液生物物理学和涂层珠聚集实验，我们证明了家庭的异嗜性特异性：所有的DSG形成粘合剂二聚体与所有的DSC，与每个DSG的亲和力特性：DSC对。来自Dsg2和Dsg3以及来自Dsc 1和Dsc 2的胞外域的晶体结构显示通过类似于嗜同性经典钙粘蛋白的链交换机制的结合。然而，保守的带电氨基酸通过同电荷排斥抑制Dsg：Dsg和Dsc：Dsc相互作用，并通过相反电荷吸引促进异嗜性Dsg：Dsc相互作用。这些结果表明，Dsg：Dsc异源二聚体代表了桥粒的基本粘附单元，并为理解桥粒组装提供了结构框架。
Desmosomes are intercellular adhesive junctions that impart strength to vertebrate tissues. Their dense, ordered intercellular attachments are formed by desmogleins (Dsgs) and desmocollins (Dscs), but the nature of trans-cellular interactions between these specialized cadherins is unclear. Here, using solution biophysics and coated-bead aggregation experiments, we demonstrate family-wise heterophilic specificity: All Dsgs form adhesive dimers with all Dscs, with affinities characteristic of each Dsg: Dsc pair. Crystal structures of ectodomains from Dsg2 and Dsg3 and from Dsc1 and Dsc2 show binding through a strand-swap mechanism similar to that of homophilic classical cadherins. However, conserved charged amino acids inhibit Dsg: Dsg and Dsc: Dsc interactions by same-charge repulsion and promote heterophilic Dsg: Dsc interactions through opposite-charge attraction. These findings show that Dsg: Dsc heterodimers represent the fundamental adhesive unit of desmosomes and provide a structural framework for understanding desmosome assembly.