Family-wide Structural and Biophysical Analysis of Binding Interactions among Non-clustered δ-Protocadherins.
X-ray crystallography
cadherin
cell adhesion
cryo-electron tomography
homophilic adhesion
neuronal cell adhesion
non-clustered protocadherins
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
25 02 2020
25 02 2020
Historique:
received:
17
08
2019
revised:
02
11
2019
accepted:
31
01
2020
entrez:
27
2
2020
pubmed:
27
2
2020
medline:
18
3
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32101743
pii: S2211-1247(20)30157-1
doi: 10.1016/j.celrep.2020.02.003
pmc: PMC7082078
mid: NIHMS1566858
pii:
doi:
Substances chimiques
Cadherins
0
Liposomes
0
Solutions
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
2655-2671.e7Subventions
Organisme : NIGMS NIH HHS
ID : F32 GM128303
Pays : United States
Organisme : NIGMS NIH HHS
ID : P41 GM103403
Pays : United States
Organisme : NIGMS NIH HHS
ID : P41 GM103310
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH114817
Pays : United States
Organisme : NCRR NIH HHS
ID : P41 RR001209
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK106548
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM118584
Pays : United States
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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