Structural requirements for the specific binding of CRABP2 to cyclin D3.

Pastok, Martyna W; Tomlinson, Charles W E; Turberville, Shannon; Baslé, Arnaud; Butler, Abbey M; Noble, Martin E M; Endicott, Jane A; Pohl, Ehmke; Tatum, Natalie J

Abstract

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. [Abstract copyright: Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.]

Citation

Pastok, M. W., Tomlinson, C. W. E., Turberville, S., Baslé, A., Butler, A. M., Noble, M. E. M., Endicott, J. A., Pohl, E., & Tatum, N. J. (online). Structural requirements for the specific binding of CRABP2 to cyclin D3. Structure, Article S0969-2126(24)00389-7. https://doi.org/10.1016/j.str.2024.09.020

• Journal Article Type: Article
• Acceptance Date: Sep 20, 2024
• Online Publication Date: Oct 16, 2024
• Deposit Date: Nov 6, 2024
• Publicly Available Date: Nov 6, 2024
• Journal: Structure
• Print ISSN: 0969-2126
• Electronic ISSN: 1878-4186
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Article Number: S0969-2126(24)00389-7
• DOI: https://doi.org/10.1016/j.str.2024.09.020
• Keywords: cyclin, alphafold, retinoic acid, ATRA, CDK4, CRABP2, regulation, CDK6
• Public URL: https://durham-repository.worktribe.com/output/3043846