6E6B

Crystal structure of the Protocadherin GammaB4 extracellular domain

6E6B の概要

• エントリーDOI: 10.2210/pdb6e6b/pdb
• 分子名称: Protocadherin gamma B4, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• 機能のキーワード: cadherin, polymer, neuronal self-recognition, neuronal self-avoidance, cell adhesion
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 146622.06

構造登録者

Goodman, K.M.,Mannepalli, S.,Bahna, F.,Honig, B.,Shapiro, L. (登録日: 2018-07-24, 公開日: 2019-04-10, 最終更新日: 2024-11-13)

主引用文献

Brasch, J.,Goodman, K.M.,Noble, A.J.,Rapp, M.,Mannepalli, S.,Bahna, F.,Dandey, V.P.,Bepler, T.,Berger, B.,Maniatis, T.,Potter, C.S.,Carragher, B.,Honig, B.,Shapiro, L.
Visualization of clustered protocadherin neuronal self-recognition complexes.
Nature, 569:280-283, 2019

PubMed Abstract: Neurite self-recognition and avoidance are fundamental properties of all nervous systems. These processes facilitate dendritic arborization, prevent formation of autapses and allow free interaction among non-self neurons. Avoidance among self neurites is mediated by stochastic cell-surface expression of combinations of about 60 isoforms of α-, β- and γ-clustered protocadherin that provide mammalian neurons with single-cell identities. Avoidance is observed between neurons that express identical protocadherin repertoires, and single-isoform differences are sufficient to prevent self-recognition. Protocadherins form isoform-promiscuous cis dimers and isoform-specific homophilic trans dimers. Although these interactions have previously been characterized in isolation, structures of full-length protocadherin ectodomains have not been determined, and how these two interfaces engage in self-recognition between neuronal surfaces remains unknown. Here we determine the molecular arrangement of full-length clustered protocadherin ectodomains in single-isoform self-recognition complexes, using X-ray crystallography and cryo-electron tomography. We determine the crystal structure of the clustered protocadherin γB4 ectodomain, which reveals a zipper-like lattice that is formed by alternating cis and trans interactions. Using cryo-electron tomography, we show that clustered protocadherin γB6 ectodomains tethered to liposomes spontaneously assemble into linear arrays at membrane contact sites, in a configuration that is consistent with the assembly observed in the crystal structure. These linear assemblies pack against each other as parallel arrays to form larger two-dimensional structures between membranes. Our results suggest that the formation of ordered linear assemblies by clustered protocadherins represents the initial self-recognition step in neuronal avoidance, and thus provide support for the isoform-mismatch chain-termination model of protocadherin-mediated self-recognition, which depends on these linear chains.

PubMed: 30971825
DOI: 10.1038/s41586-019-1089-3

実験手法

X-RAY DIFFRACTION (4.52 Å)