FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4308840315> ?p ?o ?g. }

• W4308840315 abstract "Abstract N -Methyl-D-Aspartate (NMDA) receptors are essential for many brain functions. These receptors are heterotetramers typically comprising two GluN1 subunits and two GluN2 subunits. The latter could alternate among four subtypes (N2A-N2D) and determine the functional diversity of NMDA receptors 1, 2 . For example, receptors containing N2C or N2D exhibit 50-fold lower channel open probability (Po) than those containing N2A (ref. 3–5 ). Structures of N2A- and N2B-containing receptors have been extensively characterized, providing molecular basis for understanding NMDA receptor function 6–14 . Here we report the cryo-EM structures of N1-N2D and N1-N2C di-heterotetramers (di-receptors), and N1-N2A-N2C tri-heterotetramer (tri-receptor) at a resolution up to 3.0 Å. Structural analysis showed that the bilobate N-terminal domain (NTD) in N2D adopted an intrinsic closed conformation, leading to a compact NTD tetramer in N1-N2D receptor. Functional studies further demonstrated that, in di-receptors containing N2D but not N2A or N2B, crosslinking NTD at the tetrameric interface had no effect on channel activity, while crosslinking ligand-binding domain (LBD) of two N1 protomers significantly elevated Po. Surprisingly, we found that the N1-N2C di-receptors spontaneously oscillated between symmetric and asymmetric conformation. The later one occupied a predominant population, whereby two N2C protomers exhibited distinct conformation. This asymmetry, which was also found to a lesser extent in N1-N2A di-receptor 10 , was further locked by the binding of an N2C-specific allosteric potentiator PYD-106 to a unique binding pocket between NTD and LBD in only one N2C protomer. Finally, N2A and N2C in the N1-N2A-N2C tri-receptor displayed the conformation close to that found in one protomer of N1-N2A and N1-N2C di-receptors, respectively. These findings provide a comprehensive structural understanding of diverse functional properties of major NMDA receptor subtypes." @default.
• W4308840315 created "2022-11-17" @default.
• W4308840315 creator A5002376673 @default.
• W4308840315 creator A5005450837 @default.
• W4308840315 creator A5022045214 @default.
• W4308840315 creator A5024691353 @default.
• W4308840315 creator A5027291341 @default.
• W4308840315 creator A5034604512 @default.
• W4308840315 creator A5035211521 @default.
• W4308840315 creator A5061094030 @default.
• W4308840315 creator A5064842058 @default.
• W4308840315 creator A5072319870 @default.
• W4308840315 creator A5073036406 @default.
• W4308840315 creator A5079560786 @default.
• W4308840315 creator A5082322039 @default.
• W4308840315 date "2022-11-10" @default.
• W4308840315 modified "2023-09-27" @default.
• W4308840315 title "Distinct structure and gating mechanism in diverse NMDA receptors with GluN2C and GluN2D subunits" @default.
• W4308840315 cites W1031578623 @default.
• W4308840315 cites W1505424611 @default.
• W4308840315 cites W1551983009 @default.
• W4308840315 cites W1600474674 @default.
• W4308840315 cites W1967804600 @default.
• W4308840315 cites W1974291884 @default.
• W4308840315 cites W1976499671 @default.
• W4308840315 cites W1987322407 @default.
• W4308840315 cites W1991588013 @default.
• W4308840315 cites W1996192402 @default.
• W4308840315 cites W2005777912 @default.
• W4308840315 cites W2021520922 @default.
• W4308840315 cites W2024380057 @default.
• W4308840315 cites W2029922642 @default.
• W4308840315 cites W2035687084 @default.
• W4308840315 cites W2037852973 @default.
• W4308840315 cites W2039593712 @default.
• W4308840315 cites W2041834854 @default.
• W4308840315 cites W2041902442 @default.
• W4308840315 cites W2057477511 @default.
• W4308840315 cites W2057704715 @default.
• W4308840315 cites W2061108756 @default.
• W4308840315 cites W2061259478 @default.
• W4308840315 cites W2065169750 @default.
• W4308840315 cites W2066414494 @default.
• W4308840315 cites W2072973641 @default.
• W4308840315 cites W2081693079 @default.
• W4308840315 cites W2082464161 @default.
• W4308840315 cites W2086708755 @default.
• W4308840315 cites W2086812659 @default.
• W4308840315 cites W2089094370 @default.
• W4308840315 cites W2099311604 @default.
• W4308840315 cites W2100193366 @default.
• W4308840315 cites W2104234755 @default.
• W4308840315 cites W2109154308 @default.
• W4308840315 cites W2109572831 @default.
• W4308840315 cites W2142978864 @default.
• W4308840315 cites W2144081223 @default.
• W4308840315 cites W2152301430 @default.
• W4308840315 cites W2162454135 @default.
• W4308840315 cites W2206954826 @default.
• W4308840315 cites W2319385595 @default.
• W4308840315 cites W2332332954 @default.
• W4308840315 cites W2343219805 @default.
• W4308840315 cites W2469449201 @default.
• W4308840315 cites W2519837467 @default.
• W4308840315 cites W2548809643 @default.
• W4308840315 cites W2555870966 @default.
• W4308840315 cites W2587625522 @default.
• W4308840315 cites W2590999072 @default.
• W4308840315 cites W2593511418 @default.
• W4308840315 cites W2606915259 @default.
• W4308840315 cites W2771915833 @default.
• W4308840315 cites W2786390877 @default.
• W4308840315 cites W2789629208 @default.
• W4308840315 cites W2796905767 @default.
• W4308840315 cites W2811141452 @default.
• W4308840315 cites W2884221774 @default.
• W4308840315 cites W2894702920 @default.
• W4308840315 cites W2900144052 @default.
• W4308840315 cites W2950967305 @default.
• W4308840315 cites W2964967299 @default.
• W4308840315 cites W2971253736 @default.
• W4308840315 cites W2990587446 @default.
• W4308840315 cites W3015437409 @default.
• W4308840315 cites W3040661713 @default.
• W4308840315 cites W3048946691 @default.
• W4308840315 cites W3083406432 @default.
• W4308840315 cites W3119433594 @default.
• W4308840315 cites W3175556239 @default.
• W4308840315 cites W3183790491 @default.
• W4308840315 cites W3214054678 @default.
• W4308840315 cites W3214881753 @default.
• W4308840315 cites W4232874707 @default.
• W4308840315 cites W4246043393 @default.
• W4308840315 cites W4286587770 @default.
• W4308840315 cites W4307658415 @default.
• W4308840315 doi "https://doi.org/10.1101/2022.11.09.514853" @default.
• W4308840315 hasPublicationYear "2022" @default.
• W4308840315 type Work @default.
• W4308840315 citedByCount "0" @default.
• W4308840315 crossrefType "posted-content" @default.

• next