8POI

Molecular Docking of SPF30 Tudor domain with synthetic inhibitor 4-(pyridin-2-yl)thiazol-2-amine

Summary for 8POI

• Entry DOI: 10.2210/pdb8poi/pdb
• NMR Information: BMRB: 34831
• Descriptor: Survival of motor neuron-related-splicing factor 30, 4-pyridin-2-yl-1,3-thiazol-2-amine (2 entities in total)
• Functional Keywords: tudor domain, complex, inhibitor, rna binding protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 7112.74

Authors

Borggraefe, J.,Gaussmann, S.,Sattler, M. (deposition date: 2023-07-04, release date: 2023-08-23, Last modification date: 2023-08-30)

Primary citation

Enders, L.,Siklos, M.,Borggrafe, J.,Gaussmann, S.,Koren, A.,Malik, M.,Tomek, T.,Schuster, M.,Reinis, J.,Hahn, E.,Rukavina, A.,Reicher, A.,Casteels, T.,Bock, C.,Winter, G.E.,Hannich, J.T.,Sattler, M.,Kubicek, S.
Pharmacological perturbation of the phase-separating protein SMNDC1.
Nat Commun, 14:4504-4504, 2023

PubMed Abstract: SMNDC1 is a Tudor domain protein that recognizes di-methylated arginines and controls gene expression as an essential splicing factor. Here, we study the specific contributions of the SMNDC1 Tudor domain to protein-protein interactions, subcellular localization, and molecular function. To perturb the protein function in cells, we develop small molecule inhibitors targeting the dimethylarginine binding pocket of the SMNDC1 Tudor domain. We find that SMNDC1 localizes to phase-separated membraneless organelles that partially overlap with nuclear speckles. This condensation behavior is driven by the unstructured C-terminal region of SMNDC1, depends on RNA interaction and can be recapitulated in vitro. Inhibitors of the protein's Tudor domain drastically alter protein-protein interactions and subcellular localization, causing splicing changes for SMNDC1-dependent genes. These compounds will enable further pharmacological studies on the role of SMNDC1 in the regulation of nuclear condensates, gene regulation and cell identity.

PubMed: 37587144
DOI: 10.1038/s41467-023-40124-0

Experimental method

SOLUTION NMR