Matches in SemOpenAlex for { <https://semopenalex.org/work/W3035529249> ?p ?o ?g. }
- W3035529249 abstract "ABSTRACT NMDA receptors are excitatory channels with critical functions in the physiology of central synapses. Their activation reaction proceeds as a series of kinetically distinguishable, reversible steps, whose structural bases are of current interest. Very likely, the earliest steps in the activation reaction include glutamate binding to and compression of the ligand-binding domain. Later, three short linkers transduce this movement to open the gate by mechanical coupling with transmembrane helices. Here, we used double-mutant cycle analyses to demonstrate that a direct chemical interaction between GluN1-I642 (on M3) and GluN2A-L550 (on L1-M1) stabilizes receptors after they have opened, and therefore represents one of the structural changes that occur late in the activation reaction. This native interaction extends the current decay, and its absence predicts deficits in charge transfer by GluN1-I642L, a pathogenic human variant. SIGNIFICANCE STATEMENT NMDA receptors are glutamatergic channels whose activations control the strength of excitatory synapses in the central nervous system. Agonist binding initiates a complex activation reaction that consists of a stepwise sequence of reversible isomerizations. In addition to previously identified steps in this series, which include agonist-induced closure of the ligand-binding lobes, and the subsequent mechanical pulling by the ligand-binding domain on the gate-forming transmembrane helix, we identify a new cross-subunit interaction, which stabilizes open receptors and slows the rate of the current decay. Naturally occurring NMDA receptor variants lacking this interaction are pathogenic." @default.
- W3035529249 created "2020-06-19" @default.
- W3035529249 creator A5005450837 @default.
- W3035529249 creator A5008685938 @default.
- W3035529249 creator A5045628900 @default.
- W3035529249 creator A5049050864 @default.
- W3035529249 creator A5051311631 @default.
- W3035529249 date "2020-06-09" @default.
- W3035529249 modified "2023-09-26" @default.
- W3035529249 title "Cross-subunit Interactions that Stabilize Open States Mediate Gating in NMDA Receptors" @default.
- W3035529249 cites W1969723894 @default.
- W3035529249 cites W1974988689 @default.
- W3035529249 cites W1975129786 @default.
- W3035529249 cites W1976234796 @default.
- W3035529249 cites W1976499671 @default.
- W3035529249 cites W1978121125 @default.
- W3035529249 cites W1990771438 @default.
- W3035529249 cites W1991794210 @default.
- W3035529249 cites W2008768196 @default.
- W3035529249 cites W2009667219 @default.
- W3035529249 cites W2021520922 @default.
- W3035529249 cites W2028741068 @default.
- W3035529249 cites W2029667189 @default.
- W3035529249 cites W2031812418 @default.
- W3035529249 cites W2035826968 @default.
- W3035529249 cites W2037852973 @default.
- W3035529249 cites W2039593712 @default.
- W3035529249 cites W2041638382 @default.
- W3035529249 cites W2043901383 @default.
- W3035529249 cites W2048393820 @default.
- W3035529249 cites W2053343996 @default.
- W3035529249 cites W2053980736 @default.
- W3035529249 cites W2063398239 @default.
- W3035529249 cites W2066414494 @default.
- W3035529249 cites W2067174909 @default.
- W3035529249 cites W2068653092 @default.
- W3035529249 cites W2071908149 @default.
- W3035529249 cites W2072973641 @default.
- W3035529249 cites W2073896916 @default.
- W3035529249 cites W2075494942 @default.
- W3035529249 cites W2081667420 @default.
- W3035529249 cites W2081693079 @default.
- W3035529249 cites W2083517299 @default.
- W3035529249 cites W2087600888 @default.
- W3035529249 cites W2089094370 @default.
- W3035529249 cites W2089365361 @default.
- W3035529249 cites W2097775366 @default.
- W3035529249 cites W2099000716 @default.
- W3035529249 cites W2109154308 @default.
- W3035529249 cites W2115248525 @default.
- W3035529249 cites W2116635659 @default.
- W3035529249 cites W2118200955 @default.
- W3035529249 cites W2127637463 @default.
- W3035529249 cites W2129434797 @default.
- W3035529249 cites W2132109794 @default.
- W3035529249 cites W2134762386 @default.
- W3035529249 cites W2138397305 @default.
- W3035529249 cites W2142456569 @default.
- W3035529249 cites W2146225704 @default.
- W3035529249 cites W2149525061 @default.
- W3035529249 cites W2150333097 @default.
- W3035529249 cites W2150981663 @default.
- W3035529249 cites W2154114860 @default.
- W3035529249 cites W2160544821 @default.
- W3035529249 cites W2162454135 @default.
- W3035529249 cites W2163922059 @default.
- W3035529249 cites W2168269595 @default.
- W3035529249 cites W2206954826 @default.
- W3035529249 cites W2306370307 @default.
- W3035529249 cites W2334567622 @default.
- W3035529249 cites W2335185919 @default.
- W3035529249 cites W2343219805 @default.
- W3035529249 cites W2394926658 @default.
- W3035529249 cites W2494945266 @default.
- W3035529249 cites W2550618833 @default.
- W3035529249 cites W2572516786 @default.
- W3035529249 cites W2590999072 @default.
- W3035529249 cites W2595054512 @default.
- W3035529249 cites W2686272088 @default.
- W3035529249 cites W2751117505 @default.
- W3035529249 cites W2795778689 @default.
- W3035529249 cites W2797071919 @default.
- W3035529249 cites W2884221774 @default.
- W3035529249 cites W2890312008 @default.
- W3035529249 cites W2905207755 @default.
- W3035529249 cites W2999911279 @default.
- W3035529249 cites W3013791295 @default.
- W3035529249 cites W3029570638 @default.
- W3035529249 cites W3095866415 @default.
- W3035529249 doi "https://doi.org/10.1101/2020.06.08.140525" @default.
- W3035529249 hasPublicationYear "2020" @default.
- W3035529249 type Work @default.
- W3035529249 sameAs 3035529249 @default.
- W3035529249 citedByCount "1" @default.
- W3035529249 countsByYear W30355292492020 @default.
- W3035529249 crossrefType "posted-content" @default.
- W3035529249 hasAuthorship W3035529249A5005450837 @default.
- W3035529249 hasAuthorship W3035529249A5008685938 @default.
- W3035529249 hasAuthorship W3035529249A5045628900 @default.
- W3035529249 hasAuthorship W3035529249A5049050864 @default.