6PER

Crystal Structure of Ligand-Free iSeroSnFR

Summary for 6PER

• Entry DOI: 10.2210/pdb6per/pdb
• Descriptor: iSeroSnFR, a soluble, genetically-encoded fluorescent sensor for serotonin, 1,2-ETHANEDIOL (3 entities in total)
• Functional Keywords: fluorescent sensor, serotonin binding protein, biosensor, fluorescent protein
• Biological source: Thermoanaerobacter sp. X513
• Total number of polymer chains: 1
• Total formula weight: 62570.82

Authors

Hartanto, S.,Tian, L.,Fisher, A.J. (deposition date: 2019-06-20, release date: 2020-06-24, Last modification date: 2024-10-09)

Primary citation

Unger, E.K.,Keller, J.P.,Altermatt, M.,Liang, R.,Matsui, A.,Dong, C.,Hon, O.J.,Yao, Z.,Sun, J.,Banala, S.,Flanigan, M.E.,Jaffe, D.A.,Hartanto, S.,Carlen, J.,Mizuno, G.O.,Borden, P.M.,Shivange, A.V.,Cameron, L.P.,Sinning, S.,Underhill, S.M.,Olson, D.E.,Amara, S.G.,Temple Lang, D.,Rudnick, G.,Marvin, J.S.,Lavis, L.D.,Lester, H.A.,Alvarez, V.A.,Fisher, A.J.,Prescher, J.A.,Kash, T.L.,Yarov-Yarovoy, V.,Gradinaru, V.,Looger, L.L.,Tian, L.
Directed Evolution of a Selective and Sensitive Serotonin Sensor via Machine Learning.
Cell, 183:1986-2002.e26, 2020

PubMed Abstract: Serotonin plays a central role in cognition and is the target of most pharmaceuticals for psychiatric disorders. Existing drugs have limited efficacy; creation of improved versions will require better understanding of serotonergic circuitry, which has been hampered by our inability to monitor serotonin release and transport with high spatial and temporal resolution. We developed and applied a binding-pocket redesign strategy, guided by machine learning, to create a high-performance, soluble, fluorescent serotonin sensor (iSeroSnFR), enabling optical detection of millisecond-scale serotonin transients. We demonstrate that iSeroSnFR can be used to detect serotonin release in freely behaving mice during fear conditioning, social interaction, and sleep/wake transitions. We also developed a robust assay of serotonin transporter function and modulation by drugs. We expect that both machine-learning-guided binding-pocket redesign and iSeroSnFR will have broad utility for the development of other sensors and in vitro and in vivo serotonin detection, respectively.

PubMed: 33333022
DOI: 10.1016/j.cell.2020.11.040

Experimental method

X-RAY DIFFRACTION (2.1 Å)