Structure of the planar cell polarity cadherins Fat4 and Dachsous1.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
16 02 2023
16 02 2023
Historique:
received:
31
08
2022
accepted:
01
02
2023
entrez:
16
2
2023
pubmed:
17
2
2023
medline:
22
2
2023
Statut:
epublish
Résumé
The atypical cadherins Fat and Dachsous are key regulators of cell growth and animal development. In contrast to classical cadherins, which form homophilic interactions to segregate cells, Fat and Dachsous cadherins form heterophilic interactions to induce cell polarity within tissues. Here, we determine the co-crystal structure of the human homologs Fat4 and Dachsous1 (Dchs1) to establish the molecular basis for Fat-Dachsous interactions. The binding domains of Fat4 and Dchs1 form an extended interface along extracellular cadherin (EC) domains 1-4 of each protein. Biophysical measurements indicate that Fat4-Dchs1 affinity is among the highest reported for cadherin superfamily members, which is attributed to an extensive network of salt bridges not present in structurally similar protocadherin homodimers. Furthermore, modeling suggests that unusual extracellular phosphorylation modifications directly modulate Fat-Dachsous binding by introducing charged contacts across the interface. Collectively, our analyses reveal how the molecular architecture of Fat4-Dchs1 enables them to form long-range, high-affinity interactions to maintain planar cell polarity.
Identifiants
pubmed: 36797229
doi: 10.1038/s41467-023-36435-x
pii: 10.1038/s41467-023-36435-x
pmc: PMC9935876
doi:
Substances chimiques
Cadherins
0
FAT4 protein, human
0
Tumor Suppressor Proteins
0
CDHR6 protein, human
0
Cadherin Related Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
891Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM133482
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA076292
Pays : United States
Informations de copyright
© 2023. The Author(s).
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