%0 Journal Article %T Interaction of Synthetic Human SLURP-1 with the Nicotinic Acetylcholine Receptors %+ Institute for Molecular Bioscience %+ Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry (IBCh RAS) %+ University of Wollongong [Australia] %+ Thammasat University (TU) %+ Récepteurs Canaux - Channel Receptors %A Durek, Thomas %A Shelukhina, Irina, V %A Tae, Han-Shen %A Thongyoo, Panumart %A Spirova, Ekaterina, N %A Kudryavtsev, Denis, S %A Kasheverov, Igor, E %A Faure, Grazyna %A Corringer, Pierre-Jean %A Craik, David, J %A Adams, David, J. %A Tsetlin, Victor, I %Z D.J.C. is an Australian Research Council Laureate Fellow (FL150100146) %Z VIT, ENS, DSK and IEK were supported by RSF grant No 16-14-00215 %Z P.-J.C., GF and IVS were supported by RFBR-CNRS grant 14-04-91051 %Z DJA was supported by an Australian Research Council Discovery Project Grant (DP150103990) %< avec comité de lecture %@ 2045-2322 %J Scientific Reports %I Nature Publishing Group %V 7 %N 1 %P 16606 %8 2017-11-30 %D 2017 %R 10.1038/s41598-017-16809-0 %M 29192197 %Z Life Sciences [q-bio] %Z Chemical SciencesJournal articles %X Human SLURP-1 is a secreted protein of the Ly6/uPAR/three-finger neurotoxin family that co-localizes with nicotinic acetylcholine receptors (nAChRs) and modulates their functions. Conflicting biological activities of SLURP-1 at various nAChR subtypes have been based on heterologously produced SLURP-1 containing N- and/or C-terminal extensions. Here, we report the chemical synthesis of the 81 amino acid residue human SLURP-1 protein, characterization of its 3D structure by NMR, and its biological activity at nAChR subtypes. Radioligand assays indicated that synthetic SLURP-1 did not compete with [ 125 I]-α-bungarotoxin (α-Bgt) binding to human neuronal α7 and Torpedo californica muscle-type nAChRs, nor to mollusk acetylcholine binding proteins (AChBP). Inhibition of human α7-mediated currents only occurred in the presence of the allosteric modulator PNU120596. In contrast, we observed robust SLURP-1 mediated inhibition of human α3β4, α4β4, α3β2 nAChRs, as well as human and rat α9α10 nAChRs. SLURP-1 inhibition of α9α10 nAChRs was accentuated at higher ACh concentrations, indicating an allosteric binding mechanism. Our results are discussed in the context of recent studies on heterologously produced SLURP-1 and indicate that N-terminal extensions of SLURP-1 may affect its activity and selectivity on its targets. In this respect, synthetic SLURP-1 appears to be a better probe for structure-function studies. %G English %2 https://pasteur.hal.science/pasteur-04102878/document %2 https://pasteur.hal.science/pasteur-04102878/file/Grazyna%20s41598-017-16809-0.pdf %L pasteur-04102878 %U https://pasteur.hal.science/pasteur-04102878 %~ PASTEUR %~ CNRS %~ TEST3-HALCNRS %~ CHAN-RECEPTORS %~ PASTEUR_UMR3571