Sandbox Reserved 1649: Difference between revisions
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<Structure load='2a5s' size='350' frame='true' align='right' caption='Crystal Structure Of The NR2A Ligand Binding Core In Complex With Glutamate' scene='Insert optional scene name here' /> | |||
== NR2A (2A5S) == | == NR2A (2A5S) == | ||
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'''Ligand binding domain (LBD)''' | '''Ligand binding domain (LBD)''' | ||
LBD is constituted of two domains S1 (located juste upstream M1 transmembrane domain) and S2 and has affinity for glutamate or sometime glycine. Positive charge of amino-group of the agonist bind to negative charges residue of the pocket D731. In [https://proteopedia.org/wiki/index.php/Glutamate_receptor_%28GluA2%29 GlurR], negative charge amino acid is a E731 and is able to form salt bridge with agonist. In NR2A D731 (which corresponds to <scene name='86/868182/D213/1'>D213</scene>) is not able to do salt bridge with amino group because aspartate is one methylene lacking to do it. Amino group of agonist is stabilized by water mediated hydrogen bonds to amino acid Y761 (which corresponds to <scene name='86/868182/Y243/1'>Y243</scene>) and E413 (which correspond to <scene name='86/868182/E14/1'>E14</scene>).<scene name='86/868182/Y243_et_e14/1'>Click here if you want to see E14 and Y243 together | LBD is constituted of two domains S1 (located juste upstream M1 transmembrane domain) and S2 and has affinity for glutamate or sometime glycine. Positive charge of amino-group of the agonist bind to negative charges residue of the pocket D731. In [https://proteopedia.org/wiki/index.php/Glutamate_receptor_%28GluA2%29 GlurR], negative charge amino acid is a E731 and is able to form salt bridge with agonist. In NR2A D731 (which corresponds to <scene name='86/868182/D213/1'>D213</scene>) is not able to do salt bridge with amino group because aspartate is one methylene lacking to do it. Amino group of agonist is stabilized by water mediated hydrogen bonds to amino acid Y761 (which corresponds to <scene name='86/868182/Y243/1'>Y243</scene>) and E413 (which correspond to <scene name='86/868182/E14/1'>E14</scene>).<scene name='86/868182/Y243_et_e14/1'>Click here if you want to see E14 and Y243 together</scene>. The high affinity for glutamate agonist may be because of van der Walls contact between γ-carboxylate group of glutamate and Y730 of S2 domain which is conserved in NR2 protein.<ref name="LBD">DOI 10.1038/nature04089</ref> Amino-group of glutamate also interacts with <scene name='86/868182/T114/1'>T114</scene> and <scene name='86/868182/S112/1'>S112</scene>. | ||
On the other hand, <scene name='86/868182/Aa_in_interaction_with_nr1/1'>amino acids</scene> from this domain interact with NR1 (see NR1/NR2A complex part). | On the other hand, <scene name='86/868182/Aa_in_interaction_with_nr1/1'>amino acids</scene> from this domain interact with NR1 (see NR1/NR2A complex part). | ||
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NR1 and NR2A are assembled in a dimer, arranged in a back-to-back fashion, thanks to interactions between three different domains on each subunit: sites I, II and III. | NR1 and NR2A are assembled in a dimer, arranged in a back-to-back fashion, thanks to interactions between three different domains on each subunit: sites I, II and III. | ||
- Site II: The link between NR2A and NR1 is made by at least three amino acids: E530 ( | - Site II: The link between NR2A and NR1 is made by at least three amino acids: E530 (E68 in LBD) makes a salt bridge with R755 of NR1, F524 (F62 in LBD) binds K531 of NR1 by a hydrogen bond on the backbone carbonyl oxygen, and P257. | ||
- Sites I and III: the binding is established by hydrophobic residues (I514 (<scene name='86/868182/I52/1'>I52 in LBD</scene>I52), V526 (<scene name='86/868182/V64/1'>V64 in LBD</scene>), L777, L780 present on helices D and J), or by polar contacts | - Sites I and III: the binding is established by hydrophobic residues (I514 (<scene name='86/868182/I52/1'>I52 in LBD</scene>I52), V526 (<scene name='86/868182/V64/1'>V64 in LBD</scene>), L777, L780 present on helices D and J), or by polar contacts | ||
