Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/103402
Title: An efficient proteome-wide strategy for discovery and characterization of cellular nucleotide-protein interactions
Authors: Lim, Yan Ting
Prabhu, Nayana
Dai, Lingyun
Go, Ka Diam
Chen, Dan
Sreekumar, Lekshmy
Egeblad, Louise
Eriksson, Staffan
Chen, Liyan
Veerappan, Saranya
Teo, Hsiang Ling
Tan, Chris Soon Heng
Lengqvist, Johan
Larsson, Andreas
Sobota, Radoslaw M.
Nordlund, Pär
Keywords: DRNTU::Science::Biological sciences
Metabolite
Protein-nucleotide Interactions
Issue Date: 2018
Source: Lim, Y. T., Prabhu, N., Dai, L., Go, K. D., Chen, D., Sreekumar, L., . . . Nordlund, P. (2018). An efficient proteome-wide strategy for discovery and characterization of cellular nucleotide-protein interactions. PLOS ONE, 13(12), e0208273-. doi:10.1371/journal.pone.0208273
Series/Report no.: PLOS ONE
Abstract: Metabolite-protein interactions define the output of metabolic pathways and regulate many cellular processes. Although diseases are often characterized by distortions in metabolic processes, efficient means to discover and study such interactions directly in cells have been lacking. A stringent implementation of proteome-wide Cellular Thermal Shift Assay (CETSA) was developed and applied to key cellular nucleotides, where previously experimentally confirmed protein-nucleotide interactions were well recaptured. Many predicted, but never experimentally confirmed, as well as novel protein-nucleotide interactions were discovered. Interactions included a range of different protein families where nucleotides serve as substrates, products, co-factors or regulators. In cells exposed to thymidine, a limiting precursor for DNA synthesis, both dose- and time-dependence of the intracellular binding events for sequentially generated thymidine metabolites were revealed. Interactions included known cancer targets in deoxyribonucleotide metabolism as well as novel interacting proteins. This stringent CETSA based strategy will be applicable for a wide range of metabolites and will therefore greatly facilitate the discovery and studies of interactions and specificities of the many metabolites in human cells that remain uncharacterized.
URI: https://hdl.handle.net/10356/103402
http://hdl.handle.net/10220/47307
DOI: 10.1371/journal.pone.0208273
Rights: © 2018 Lim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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