EMD-21193
human non-clustered delta protocadherin 10 full ectodomains on membranes tomogram 3
EMD-21193
Tomography
Map released: 11/03/2020
Last modified: 11/03/2020
Sample Organism:
Homo sapiens
Sample: trans dimers of protocadherin 10 extracellular domains formed between membranes of liposomes
Raw data: EMPIAR-10372
Deposition Authors: Brasch J, Harrisson OJ, Noble AJ, Carragher B, Potter CS, Shapiro LS
Sample: trans dimers of protocadherin 10 extracellular domains formed between membranes of liposomes
Raw data: EMPIAR-10372
Deposition Authors: Brasch J, Harrisson OJ, Noble AJ, Carragher B, Potter CS, Shapiro LS
Family-wide Structural and Biophysical Analysis of Binding Interactions among Non-clustered delta-Protocadherins.
Harrison OJ,
Brasch J,
Katsamba PS
,
Ahlsen G,
Noble AJ
,
Dan H,
Sampogna RV,
Potter CS,
Carragher B,
Honig B
,
Shapiro L
(2020) Cell Rep , 30 , 2655 - 2671.e7
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(2020) Cell Rep , 30 , 2655 - 2671.e7
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.
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.