Rotational symmetry of the structured Chip/LDB-SSDP core module of the Wnt enhanceosome.
Amino Acid Sequence
DNA-Binding Proteins
/ chemistry
Dimerization
Enhancer Elements, Genetic
Gene Expression Regulation
Humans
LIM Domain Proteins
/ chemistry
Models, Molecular
Multiprotein Complexes
/ chemistry
Promoter Regions, Genetic
Protein Binding
Protein Domains
Transcription Factors
/ chemistry
Wnt Proteins
/ genetics
Chip/LDB1-SSDP
Pygo
Wnt enhanceosome
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
15 10 2019
15 10 2019
Historique:
pubmed:
2
10
2019
medline:
31
3
2020
entrez:
2
10
2019
Statut:
ppublish
Résumé
The Chip/LIM-domain binding protein (LDB)-single-stranded DNA-binding protein (SSDP) (ChiLS) complex controls numerous cell-fate decisions in animal cells, by mediating transcription of developmental control genes via remote enhancers. ChiLS is recruited to these enhancers by lineage-specific LIM-domain proteins that bind to its Chip/LDB subunit. ChiLS recently emerged as the core module of the Wnt enhanceosome, a multiprotein complex that primes developmental control genes for timely Wnt responses. ChiLS binds to NPFxD motifs within Pygopus (Pygo) and the Osa/ARID1A subunit of the BAF chromatin remodeling complex, which could synergize with LIM proteins in tethering ChiLS to enhancers. Chip/LDB and SSDP both contain N-terminal dimerization domains that constitute the bulk of their structured cores. Here, we report the crystal structures of these dimerization domains, in part aided by DARPin chaperones. We conducted systematic surface scanning by structure-designed mutations, followed by in vitro and in vivo binding assays, to determine conserved surface residues required for binding between Chip/LDB, SSDP, and Pygo-NPFxD. Based on this, and on the 4:2 (SSDP-Chip/LDB) stoichiometry of ChiLS, we derive a highly constrained structural model for this complex, which adopts a rotationally symmetrical SSDP
Identifiants
pubmed: 31570581
pii: 1912705116
doi: 10.1073/pnas.1912705116
pmc: PMC6800368
doi:
Substances chimiques
DNA-Binding Proteins
0
LDB1 protein, human
0
LDB2 protein, human
0
LIM Domain Proteins
0
Multiprotein Complexes
0
SSBP3 protein, human
0
Transcription Factors
0
Wnt Proteins
0
Banques de données
PDB
['6S9R', '6D9T', '6S9S']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
20977-20983Subventions
Organisme : Medical Research Council
ID : MC_U105192713
Pays : United Kingdom
Organisme : Medical Research Council
ID : U105192713
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C7379/A24639
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C7379/A15291
Pays : United Kingdom
Informations de copyright
Copyright © 2019 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
The authors declare no competing interest.
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