2pr9

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(New page: 200px {{Structure |PDB= 2pr9 |SIZE=350|CAPTION= <scene name='initialview01'>2pr9</scene>, resolution 2.510&Aring; |SITE= |LIGAND= |ACTIVITY= |GENE= Ap2m1 ([htt...)
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|ACTIVITY=
|ACTIVITY=
|GENE= Ap2m1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])
|GENE= Ap2m1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])
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|DOMAIN=
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|RELATEDENTRY=[[1bw8|1BW8]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2pr9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pr9 OCA], [http://www.ebi.ac.uk/pdbsum/2pr9 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2pr9 RCSB]</span>
}}
}}
'''Mu2 adaptin subunit (AP50) of AP2 adaptor (second domain), complexed with GABAA receptor-gamma2 subunit-derived internalization peptide DEEYGYECL'''
'''Mu2 adaptin subunit (AP50) of AP2 adaptor (second domain), complexed with GABAA receptor-gamma2 subunit-derived internalization peptide DEEYGYECL'''
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==Overview==
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The regulation of the number of gamma2-subunit-containing GABA(A) receptors (GABA(A)Rs) present at synapses is critical for correct synaptic inhibition and animal behavior. This regulation occurs, in part, by the controlled removal of receptors from the membrane in clathrin-coated vesicles, but it remains unclear how clathrin recruitment to surface gamma2-subunit-containing GABA(A)Rs is regulated. Here, we identify a gamma2-subunit-specific Yxxvarphi-type-binding motif for the clathrin adaptor protein, AP2, which is located within a site for gamma2-subunit tyrosine phosphorylation. Blocking GABA(A)R-AP2 interactions via this motif increases synaptic responses within minutes. Crystallographic and biochemical studies reveal that phosphorylation of the Yxxvarphi motif inhibits AP2 binding, leading to increased surface receptor number. In addition, the crystal structure provides an explanation for the high affinity of this motif for AP2 and suggests that gamma2-subunit-containing heteromeric GABA(A)Rs may be internalized as dimers or multimers. These data define a mechanism for tyrosine kinase regulation of GABA(A)R surface levels and synaptic inhibition.
==About this Structure==
==About this Structure==
2PR9 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PR9 OCA].
2PR9 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PR9 OCA].
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==Reference==
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Regulation of synaptic inhibition by phospho-dependent binding of the AP2 complex to a YECL motif in the GABAA receptor gamma2 subunit., Kittler JT, Chen G, Kukhtina V, Vahedi-Faridi A, Gu Z, Tretter V, Smith KR, McAinsh K, Arancibia-Carcamo IL, Saenger W, Haucke V, Yan Z, Moss SJ, Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3616-21. Epub 2008 Feb 27. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18305175 18305175]
[[Category: Protein complex]]
[[Category: Protein complex]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
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[[Category: internalization peptide complex]]
[[Category: internalization peptide complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:19:31 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:39:42 2008''

Revision as of 01:39, 31 March 2008

Image:2pr9.jpg


PDB ID 2pr9

Drag the structure with the mouse to rotate
, resolution 2.510Å
Gene: Ap2m1 (Rattus norvegicus)
Related: 1BW8


Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Mu2 adaptin subunit (AP50) of AP2 adaptor (second domain), complexed with GABAA receptor-gamma2 subunit-derived internalization peptide DEEYGYECL


Overview

The regulation of the number of gamma2-subunit-containing GABA(A) receptors (GABA(A)Rs) present at synapses is critical for correct synaptic inhibition and animal behavior. This regulation occurs, in part, by the controlled removal of receptors from the membrane in clathrin-coated vesicles, but it remains unclear how clathrin recruitment to surface gamma2-subunit-containing GABA(A)Rs is regulated. Here, we identify a gamma2-subunit-specific Yxxvarphi-type-binding motif for the clathrin adaptor protein, AP2, which is located within a site for gamma2-subunit tyrosine phosphorylation. Blocking GABA(A)R-AP2 interactions via this motif increases synaptic responses within minutes. Crystallographic and biochemical studies reveal that phosphorylation of the Yxxvarphi motif inhibits AP2 binding, leading to increased surface receptor number. In addition, the crystal structure provides an explanation for the high affinity of this motif for AP2 and suggests that gamma2-subunit-containing heteromeric GABA(A)Rs may be internalized as dimers or multimers. These data define a mechanism for tyrosine kinase regulation of GABA(A)R surface levels and synaptic inhibition.

About this Structure

2PR9 is a Protein complex structure of sequences from Rattus norvegicus. Full crystallographic information is available from OCA.

Reference

Regulation of synaptic inhibition by phospho-dependent binding of the AP2 complex to a YECL motif in the GABAA receptor gamma2 subunit., Kittler JT, Chen G, Kukhtina V, Vahedi-Faridi A, Gu Z, Tretter V, Smith KR, McAinsh K, Arancibia-Carcamo IL, Saenger W, Haucke V, Yan Z, Moss SJ, Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3616-21. Epub 2008 Feb 27. PMID:18305175

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