Browse by author
Lookup NU author(s): Dr Martyna PastokORCiD, Dr Shannon TurbervilleORCiD, Dr Arnaud Basle, Professor Martin NobleORCiD, Professor Jane Endicott, Dr Susanne Pohl, Dr Natalie TatumORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2024 The Author(s). Cellular retinoic acid binding protein 2 (CRABP2) transports retinoic acid from the cytoplasm to the nucleus where it then transfers its cargo to retinoic acid receptor-containing complexes leading to activation of gene transcription. We demonstrate using purified proteins that CRABP2 is also a cyclin D3-specific binding protein and that the CRABP2 cyclin D3 binding site and the proposed CRABP2 nuclear localization sequence overlap. Both sequences are within the helix-loop-helix motif that forms a lid to the retinoic acid binding pocket. Mutations within this sequence that block both cyclin D3 and retinoic acid binding promote formation of a CRABP2 structure in which the retinoic acid binding pocket is occupied by an alternative lid conformation. Structural and functional analysis of CRABP2 and cyclin D3 mutants combined with AlphaFold models of the ternary CDK4/6-cyclin D3-CRABP2 complex supports the identification of an α-helical protein binding site on the cyclin D3 C-terminal cyclin box fold.
Author(s): Pastok MW, Tomlinson CWE, Turberville S, Butler AM, Basle A, Noble MEM, Endicott JA, Pohl E, Tatum NJ
Publication type: Article
Publication status: Published
Journal: Structure
Year: 2024
Pages: Epub ahead of print
Online publication date: 16/10/2024
Acceptance date: 20/09/2024
Date deposited: 12/11/2024
ISSN (print): 0969-2126
ISSN (electronic): 1878-4186
Publisher: Cell Press
URL: https://doi.org/10.1016/j.str.2024.09.020
DOI: 10.1016/j.str.2024.09.020
Data Access Statement: All crystallographic data have been deposited at the Protein Data Bank (PDB) https://www.rcsb.org/ and are publicly available. Accession numbers are listed in the key resources table. PDB accession codes for structures used within, but not derived from, this study: PDB: 2FRS (F15W mutant of apo-CRABP2 at 1.51 Å resolution), PDB: 2FS7 (apo-CRABP2 at 1.55 Å resolution), PDB: 1CBQ (RA-bound CRABP2 at 2.20 Å resolution), PDB: 2CBS (RO-13 6307 bound CRABP2 at 2.1 Å resolution), PDB: 2W9F (CDK4-cyclin D1 at 2.85 Å resolution), PDB: 3G33 (CDK4-cyclin D3 at 3.00 Å resolution), PDB: 7SJ3 (CDK4-cyclin D3-abemaciclib at 2.51 Å resolution). Biophysical assay (retinoid binding, HTRF, and DSF) and molecular dynamics and AlphaFold Multimer modeling data reported in this paper will be shared by the lead contact upon request. This paper does not report original code. Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.
PubMed id: 39419021
Altmetrics provided by Altmetric
