6VFU

Crystal structure of human protocadherin 19 EC1-EC4

6VFU の概要

• エントリーDOI: 10.2210/pdb6vfu/pdb
• 分子名称: Protocadherin-19, 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, alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• 機能のキーワード: cadherin extracellular region, non-clustered delta2 family, protocadherin, homophilic, adhesion/recognition calcium-dependent adhesion molecule, cell adhesion
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 144833.03

構造登録者

Harrison, O.J.,Brasch, J.,Shapiro, L. (登録日: 2020-01-06, 公開日: 2020-03-11, 最終更新日: 2024-11-13)

主引用文献

Harrison, O.J.,Brasch, J.,Katsamba, P.S.,Ahlsen, G.,Noble, A.J.,Dan, H.,Sampogna, R.V.,Potter, C.S.,Carragher, B.,Honig, B.,Shapiro, L.
Family-wide Structural and Biophysical Analysis of Binding Interactions among Non-clustered delta-Protocadherins.
Cell Rep, 30:2655-2671.e7, 2020

PubMed Abstract: Non-clustered δ1- and δ2-protocadherins, close relatives of clustered protocadherins, function in cell adhesion and motility and play essential roles in neural patterning. To understand the molecular interactions underlying these functions, we used solution biophysics to characterize binding of δ1- and δ2-protocadherins, determined crystal structures of ectodomain complexes from each family, and assessed ectodomain assembly in reconstituted intermembrane junctions by cryoelectron tomography (cryo-ET). Homophilic trans (cell-cell) interactions were preferred for all δ-protocadherins, with additional weaker heterophilic interactions observed exclusively within each subfamily. As expected, δ1- and δ2-protocadherin trans dimers formed through antiparallel EC1-EC4 interfaces, like clustered protocadherins. However, no ectodomain-mediated cis (same-cell) interactions were detectable in solution; consistent with this, cryo-ET of reconstituted junctions revealed dense assemblies lacking the characteristic order observed for clustered protocadherins. Our results define non-clustered protocadherin binding properties and their structural basis, providing a foundation for interpreting their functional roles in neural patterning.

PubMed: 32101743
DOI: 10.1016/j.celrep.2020.02.003

実験手法

X-RAY DIFFRACTION (3.5 Å)