5ZOJ

Crystal structure of human SMAD2-MAN1 complex

Summary for 5ZOJ

• Entry DOI: 10.2210/pdb5zoj/pdb
• Descriptor: Mothers against decapentaplegic homolog 2, Inner nuclear membrane protein Man1 (2 entities in total)
• Functional Keywords: transcription, complex, tgf-beta signaling, dna binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 97495.75

Authors

Miyazono, K.,Ohno, Y.,Ito, T.,Tanokura, M. (deposition date: 2018-04-13, release date: 2018-10-10, Last modification date: 2024-03-27)

Primary citation

Miyazono, K.I.,Ohno, Y.,Wada, H.,Ito, T.,Fukatsu, Y.,Kurisaki, A.,Asashima, M.,Tanokura, M.
Structural basis for receptor-regulated SMAD recognition by MAN1
Nucleic Acids Res., 46:12139-12153, 2018

PubMed Abstract: Receptor-regulated SMAD (R-SMAD: SMAD1, SMAD2, SMAD3, SMAD5 and SMAD8) proteins are key transcription factors of the transforming growth factor-β (TGF-β) superfamily of cytokines. MAN1, an integral protein of the inner nuclear membrane, is a SMAD cofactor that terminates TGF-β superfamily signals. Heterozygous loss-of-function mutations in MAN1 result in osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis. MAN1 interacts with MAD homology 2 (MH2) domains of R-SMAD proteins using its C-terminal U2AF homology motif (UHM) domain and UHM ligand motif (ULM) and facilitates R-SMAD dephosphorylation. Here, we report the structural basis for R-SMAD recognition by MAN1. The SMAD2-MAN1 and SMAD1-MAN1 complex structures show that an intramolecular UHM-ULM interaction of MAN1 forms a hydrophobic surface that interacts with a hydrophobic surface among the H2 helix, the strands β8 and β9, and the L3 loop of the MH2 domains of R-SMAD proteins. The complex structures also show the mechanism by which SMAD cofactors distinguish R-SMAD proteins that possess a highly conserved molecular surface.

PubMed: 30321401
DOI: 10.1093/nar/gky925

Experimental method

X-RAY DIFFRACTION (2.794 Å)