Structural basis for tunable affinity and specificity of LxCxE-dependent protein interactions with the retinoblastoma protein family.
Rb protein
cell-cycle control
gene regulation
p107 protein
protein-protein interactions
short linear motif
tumor suppressor
viral oncogene
Journal
Structure (London, England : 1993)
ISSN: 1878-4186
Titre abrégé: Structure
Pays: United States
ID NLM: 101087697
Informations de publication
Date de publication:
01 09 2022
01 09 2022
Historique:
received:
08
02
2022
revised:
25
04
2022
accepted:
25
05
2022
pubmed:
19
6
2022
medline:
9
9
2022
entrez:
18
6
2022
Statut:
ppublish
Résumé
The retinoblastoma protein (Rb) and its homologs p107 and p130 are critical regulators of gene expression during the cell cycle and are commonly inactivated in cancer. Rb proteins use their "pocket domain" to bind an LxCxE sequence motif in other proteins, many of which function with Rb proteins to co-regulate transcription. Here, we present binding data and crystal structures of the p107 pocket domain in complex with LxCxE peptides from the transcriptional co-repressor proteins HDAC1, ARID4A, and EID1. Our results explain why Rb and p107 have weaker affinity for cellular LxCxE proteins compared with the E7 protein from human papillomavirus, which has been used as the primary model for understanding LxCxE motif interactions. Our structural and mutagenesis data also identify and explain differences in Rb and p107 affinities for some LxCxE-containing sequences. Our study provides new insights into how Rb proteins bind their cell partners with varying affinity and specificity.
Identifiants
pubmed: 35716663
pii: S0969-2126(22)00228-3
doi: 10.1016/j.str.2022.05.019
pmc: PMC9444907
mid: NIHMS1817661
pii:
doi:
Substances chimiques
Repressor Proteins
0
Retinoblastoma Protein
0
Retinoblastoma-Like Protein p130
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
1340-1353.e3Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM124148
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM127707
Pays : United States
Organisme : NIGMS NIH HHS
ID : T34 GM007910
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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