@article {2023|2164,
	title = {Molecular determinants of inhibition of UCP1-mediated respiratory uncoupling.},
	journal = {Nat Commun},
	volume = {14},
	year = {2023},
	month = {2023 May 05},
	pages = {2594},
	abstract = {<p>Brown adipose tissue expresses uncoupling protein 1 (UCP1), which dissipates energy as heat, making it a target for treating metabolic disorders. Here, we investigate how purine nucleotides inhibit respiration uncoupling by UCP1. Our molecular simulations predict that GDP and GTP bind UCP1 in the common substrate binding site in an upright orientation, where the base moiety interacts with conserved residues R92 and E191. We identify a triplet of uncharged residues, F88/I187/W281, forming hydrophobic contacts with nucleotides. In yeast spheroplast respiration assays, both I187A and W281A mutants increase the fatty acid-induced uncoupling activity of UCP1 and partially suppress the inhibition of UCP1 activity by nucleotides. The F88A/I187A/W281A triple mutant is overactivated by fatty acids even at high concentrations of purine nucleotides. In simulations, E191 and W281 interact with purine but not pyrimidine bases. These results provide a molecular understanding of the selective inhibition of UCP1 by purine nucleotides.</p>
},
	keywords = {Adipose Tissue, Brown, Fatty Acids, Ion Channels, Membrane Proteins, Mitochondrial Proteins, Purine Nucleotides, Saccharomyces cerevisiae, Uncoupling Protein 1},
	issn = {2041-1723},
	doi = {10.1038/s41467-023-38219-9},
	author = {Gagelin, Antoine and Largeau, Corentin and Masscheleyn, Sandrine and Piel, Mathilde S and Calder{\'o}n-Mora, Daniel and Bouillaud, Fr{\'e}d{\'e}ric and J{\'e}r{\^o}me H{\'e}nin and Miroux, Bruno}
}
@article {2010|1789,
	title = {Single-spanning transmembrane domains in cell growth and cell-cell interactions: More than meets the eye?},
	journal = {Cell Adh. Migr.},
	volume = {4},
	number = {2},
	year = {2010},
	month = {apr},
	pages = {313{\textendash}324},
	abstract = {<p>As a whole, integral membrane proteins represent about one third of sequenced genomes, and more than 50\% of currently available drugs target membrane proteins, often cell surface receptors. Some membrane protein classes, with a defined number of transmembrane (TM) helices, are receiving much attention because of their great functional and pharmacological importance, such as G protein-coupled receptors possessing 7 TM segments. Although they represent roughly half of all membrane proteins, bitopic proteins (with only 1 TM helix) have so far been less well characterized. Though they include many essential families of receptors, such as adhesion molecules and receptor tyrosine kinases, many of which are excellent targets for biopharmaceuticals (peptides, antibodies, et al.). A growing body of evidence suggests a major role for interactions between TM domains of these receptors in signaling, through homo and heteromeric associations, conformational changes, assembly of signaling platforms, etc. Significantly, mutations within single domains are frequent in human disease, such as cancer or developmental disorders. This review attempts to give an overview of current knowledge about these interactions, from structural data to therapeutic perspectives, focusing on bitopic proteins involved in cell signaling.</p>},
	keywords = {Animals, Biological, Humans, Membrane Proteins, Models, Protein Structure, Secondary, Signal Transduction, Tertiary},
	issn = {1933-6926},
	doi = {10.4161/cam.4.2.12430},
	author = {Pierre Hubert and Paul Sawma and Jean-Pierre Duneau and Jonathan Khao and J{\'e}r{\^o}me H{\'e}nin and Dominique Bagnard and James Sturgis}
}
