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• W4294597773 abstract "Abstract The serotonin transporter (SERT) is a member of the SLC6 neurotransmitter transporter family that mediates serotonin reuptake at presynaptic nerve terminals. SERT is the target of both therapeutic antidepressant drugs and illicit psychostimulant substances such as cocaine and methamphetamines, which are small molecules that perturb normal serotonergic transmission by interfering with serotonin transport. Despite decades of studies, important functional aspects of SERT such as the oligomerization state of native SERT and its interactions with potential proteins remain unresolved. Here we develop methods to isolate SERT from porcine brain (pSERT) using a mild, non-ionic detergent, utilize fluorescence- detection size-exclusion chromatography to investigate its oligomerization state and interactions with other proteins, and employ single-particle cryo-electron microscopy to elucidate the structures of pSERT in complexes with methamphetamine or cocaine, providing structural insights into psychostimulant recognition and accompanying pSERT conformations. Methamphetamine and cocaine both bind to SERT central site, stabilizing the transporter in an outward open conformation. We also identify densities attributable to multiple cholesterol or cholesteryl hemisuccinate (CHS) molecules, as well as to a detergent molecule bound to SERT allosteric site. Under our conditions of isolation, we find that pSERT is best described as a monomeric entity, isolated without interacting proteins, and is ensconced by multiple cholesterol or CHS molecules. Significance The serotonin transporter (SERT) is the target of antidepressants and illicit psychostimulants. Despite its importance in the nervous, cardiovascular and gastrointestinal systems, there is no direct knowledge of SERT’s oligomerization state(s) and interactions with other proteins. Here, we develop methods to isolate porcine SERT (pSERT) from native brain tissue in the presence of a mild, non-ionic detergent, and investigated its properties by biochemical, structural and computational methods. We show how cocaine and methamphetamine exert their pharmacological effect on SERT, binding to a site halfway across the membrane-spanning region of the transporter, stabilizing pSERT in an outward open conformation. pSERT is best described as a monomeric entity, requiring neither oligomerization or additional proteins for its structure or function." @default.
• W4294597773 created "2022-09-05" @default.
• W4294597773 creator A5012717506 @default.
• W4294597773 creator A5046732533 @default.
• W4294597773 creator A5086741446 @default.
• W4294597773 creator A5088125571 @default.
• W4294597773 date "2022-09-05" @default.
• W4294597773 modified "2023-09-28" @default.
• W4294597773 title "Structures and membrane interactions of native serotonin transporter in complexes with psychostimulants" @default.
• W4294597773 cites W1529512098 @default.
• W4294597773 cites W1738174632 @default.
• W4294597773 cites W1775574947 @default.
• W4294597773 cites W1858760132 @default.
• W4294597773 cites W1908164157 @default.
• W4294597773 cites W1964672651 @default.
• W4294597773 cites W1965533027 @default.
• W4294597773 cites W1966357919 @default.
• W4294597773 cites W1967751997 @default.
• W4294597773 cites W1970124769 @default.
• W4294597773 cites W1972342888 @default.
• W4294597773 cites W1972758026 @default.
• W4294597773 cites W1976343688 @default.
• W4294597773 cites W1976499671 @default.
• W4294597773 cites W1976855232 @default.
• W4294597773 cites W1977199897 @default.
• W4294597773 cites W1985176332 @default.
• W4294597773 cites W1985814681 @default.
• W4294597773 cites W1988224529 @default.
• W4294597773 cites W1997432723 @default.
• W4294597773 cites W2018764383 @default.
• W4294597773 cites W2021520922 @default.
• W4294597773 cites W2023125871 @default.
• W4294597773 cites W2029667189 @default.
• W4294597773 cites W2033921021 @default.
• W4294597773 cites W2034514158 @default.
• W4294597773 cites W2036328114 @default.
• W4294597773 cites W2039581146 @default.
• W4294597773 cites W2044171421 @default.
• W4294597773 cites W2045520658 @default.
• W4294597773 cites W2046508842 @default.
• W4294597773 cites W2050367290 @default.
• W4294597773 cites W2055821738 @default.
• W4294597773 cites W2056033864 @default.
• W4294597773 cites W2063469071 @default.
• W4294597773 cites W2066414494 @default.
• W4294597773 cites W2067174909 @default.
• W4294597773 cites W2068630247 @default.
• W4294597773 cites W2069069287 @default.
• W4294597773 cites W2069288279 @default.
• W4294597773 cites W2070430670 @default.
• W4294597773 cites W2070753604 @default.
• W4294597773 cites W2074631079 @default.
• W4294597773 cites W2080756480 @default.
• W4294597773 cites W2082547742 @default.
• W4294597773 cites W2084290194 @default.
• W4294597773 cites W2085732441 @default.
• W4294597773 cites W2087277719 @default.
• W4294597773 cites W2089814223 @default.
• W4294597773 cites W2091649030 @default.
• W4294597773 cites W2093383843 @default.
• W4294597773 cites W2096644570 @default.
• W4294597773 cites W2103945336 @default.
• W4294597773 cites W2104234755 @default.
• W4294597773 cites W2104622728 @default.
• W4294597773 cites W2106140689 @default.
• W4294597773 cites W2107617181 @default.
• W4294597773 cites W2112154906 @default.
• W4294597773 cites W2129495111 @default.
• W4294597773 cites W2135190897 @default.
• W4294597773 cites W2139600517 @default.
• W4294597773 cites W2140831051 @default.
• W4294597773 cites W2144297861 @default.
• W4294597773 cites W2150981663 @default.
• W4294597773 cites W2162746575 @default.
• W4294597773 cites W2167210425 @default.
• W4294597773 cites W2215904362 @default.
• W4294597773 cites W2316392160 @default.
• W4294597773 cites W2322796880 @default.
• W4294597773 cites W2330799739 @default.
• W4294597773 cites W2409887094 @default.
• W4294597773 cites W2555870966 @default.
• W4294597773 cites W2559453001 @default.
• W4294597773 cites W2579463126 @default.
• W4294597773 cites W2587625522 @default.
• W4294597773 cites W2593511418 @default.
• W4294597773 cites W2768114066 @default.
• W4294597773 cites W2770119180 @default.
• W4294597773 cites W2784627779 @default.
• W4294597773 cites W2788196490 @default.
• W4294597773 cites W2805395361 @default.
• W4294597773 cites W2807485763 @default.
• W4294597773 cites W2923284820 @default.
• W4294597773 cites W2940516695 @default.
• W4294597773 cites W2950967305 @default.
• W4294597773 cites W2952236080 @default.
• W4294597773 cites W2969316614 @default.
• W4294597773 cites W2973457155 @default.
• W4294597773 cites W2977535769 @default.
• W4294597773 cites W3039210466 @default.
• W4294597773 cites W3048273726 @default.

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