4gpa

From Proteopedia

(Difference between revisions)

Revision as of 16:02, 24 December 2014

High resolution structure of the GluA4 N-terminal domain (NTD)

Structural highlights

4gpa is a 1 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	3hsy, 3o21
Gene:	Glur4, Gria4 (Rattus norvegicus)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[GRIA4_RAT] Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate (By similarity).^[1] ^[2] ^[3]

Publication Abstract from PubMed

Ionotropic glutamate receptors (iGluRs) harbor two extracellular domains: the membrane-proximal ligand-binding domain (LBD) and the distal N-terminal domain (NTD). These are involved in signal sensing: the LBD binds L-glutamate, which activates the receptor channel. Ligand binding to the NTD modulates channel function in the NMDA receptor subfamily of iGluRs, which has not been observed for the AMPAR subfamily to date. Structural data suggest that AMPAR NTDs are packed into tight dimers and have lost their signaling potential. Here, we assess NTD dynamics from both subfamilies, using a variety of computational tools. We describe the conformational motions that underly NMDAR NTD allosteric signaling. Unexpectedly, AMPAR NTDs are capable of undergoing similar dynamics; although dimerization imposes restrictions, the two subfamilies sample similar, interconvertible conformational subspaces. Finally, we solve the crystal structure of AMPAR GluA4 NTD, and combined with molecular dynamics simulations, we characterize regions pivotal for an as-yet-unexplored dynamic spectrum of AMPAR NTDs.

Comparative Dynamics of NMDA- and AMPA-Glutamate Receptor N-Terminal Domains.,Dutta A, Shrivastava IH, Sukumaran M, Greger IH, Bahar I Structure. 2012 Sep 5. PMID:22959625^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Pasternack A, Coleman SK, Fethiere J, Madden DR, LeCaer JP, Rossier J, Pasternack M, Keinanen K. Characterization of the functional role of the N-glycans in the AMPA receptor ligand-binding domain. J Neurochem. 2003 Mar;84(5):1184-92. PMID:12603841
↑ Gill A, Birdsey-Benson A, Jones BL, Henderson LP, Madden DR. Correlating AMPA receptor activation and cleft closure across subunits: crystal structures of the GluR4 ligand-binding domain in complex with full and partial agonists. Biochemistry. 2008 Dec 30;47(52):13831-41. PMID:19102704 doi:10.1021/bi8013196
↑ Birdsey-Benson A, Gill A, Henderson LP, Madden DR. Enhanced efficacy without further cleft closure: reevaluating twist as a source of agonist efficacy in AMPA receptors. J Neurosci. 2010 Jan 27;30(4):1463-70. PMID:20107073 doi:30/4/1463
↑ Dutta A, Shrivastava IH, Sukumaran M, Greger IH, Bahar I. Comparative Dynamics of NMDA- and AMPA-Glutamate Receptor N-Terminal Domains. Structure. 2012 Sep 5. PMID:22959625 doi:http://dx.doi.org/10.1016/j.str.2012.08.012

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4gpa"

@@ Line 8: / Line 8: @@
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4gpa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gpa OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4gpa RCSB], [http://www.ebi.ac.uk/pdbsum/4gpa PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/GRIA4_RAT GRIA4_RAT]] Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate (By similarity).<ref>PMID:12603841</ref> <ref>PMID:19102704</ref> <ref>PMID:20107073</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

4gpa

From Proteopedia

Revision as of 16:02, 24 December 2014

High resolution structure of the GluA4 N-terminal domain (NTD)

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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