PDBsum entry 2uxa

Membrane protein

PDB id: 2uxa

Contents

Protein chains

261 a.a. *

Ligands

GLU ×3

Metals

_ZN ×5

Waters ×415

* Residue conservation analysis

PDB id:

2uxa

Name:

Membrane protein

Title:

Crystal structure of the glur2-flip ligand binding domain, r/g unedited.

Structure:

Glutamate receptor subunit glur2-flip. Chain: a, b, c. Fragment: ligand binding core, residues 412-527,653-795. Synonym: glutamate receptor 2, glur-2, glur-b, glur-k2, glutamate receptor ionotropic, ampa 2, ampa-selective glutamate receptor, 2glur2-flip. Engineered: yes

Source:

Rattus norvegicus. Rat. Organism_taxid: 10116. Organ: brain. Tissue: brain. Cell: neuron. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.38Å R-factor: 0.179 R-free: 0.265

Authors:

I.H.Greger,P.Akamine,L.Khatri,E.B.Ziff

Key ref:

I.H.Greger et al. (2006). Developmentally regulated, combinatorial RNA processing modulates AMPA receptor biogenesis. Neuron, 51, 85-97. PubMed id: 16815334 DOI: 10.1016/j.neuron.2006.05.020

Date:

27-Mar-07 Release date: 10-Apr-07

Protein chains

P19491  (GRIA2_RAT) -  Glutamate receptor 2 from Rattus norvegicus

Seq: 883 a.a.

Struc: 261 a.a.*

* PDB and UniProt seqs differ at 7 residue positions (black crosses)

DOI no: 10.1016/j.neuron.2006.05.020

Neuron 51:85-97 (2006)

PubMed id: 16815334

Developmentally regulated, combinatorial RNA processing modulates AMPA receptor biogenesis.

I.H.Greger, P.Akamine, L.Khatri, E.B.Ziff.

ABSTRACT

The subunit composition determines AMPA receptor (AMPA-R) function and trafficking. Mechanisms underlying channel assembly are thus central to the efficacy and plasticity of glutamatergic synapses. We previously showed that RNA editing at the Q/R site of the GluR2 subunit contributes to the assembly of AMPA-R heteromers by attenuating formation of GluR2 homotetramers. Here we report that this function of the Q/R site depends on subunit contacts between adjacent ligand binding domains (LBDs). Changes of LBD interface contacts alter GluR2 assembly properties, forward traffic, and expression at synapses. Interestingly, developmentally regulated RNA editing within the LBD (at the R/G site) produces analogous effects. Our data reveal that editing to glycine reduces the self-assembly competence of this critical subunit and slows GluR2 maturation in the endoplasmic reticulum (ER). Therefore, RNA editing sites, located at strategic subunit interfaces, shape AMPA-R assembly and trafficking in a developmentally regulated manner.

Selected figure(s)

Figure 4.
Figure 4. The Crystal Structure of the R2i-R LBD Reveals Closely Opposed Arg743 Side Chains; C ζ Distance = 3.9 Å
(A) Sequence alignment depicting amino acid changes between flip and flop, starting at position 744; the R/G site (743) is shown in bold. Alternative residues are indicated in color. Helices J and K (light blue bars) are drawn above the sequences. Note that the cluster of changes comprising position 775–779 is not included in the structure.
(B) Side view of the glutamate-bound flip/R LBD dimer. The two subunits are color coded (chain A in cyan, chain C in yellow). Arg743 is indicated in stick.
(C) Superposition of the flip/R (yellow) and flop/G LBDs (gray; top view). Alternative residues, 743–745, are shown in stick: flip residues, black; flop residues, white; positions are indicated on one protomer only. Helices D and J are denoted.
(D) Fo-Fc electron densities for Arg743 side chains. Contour level was 0.16 e/Å^3. The figure was drawn with CCP4mg.

Figure 5.
Figure 5. Electrostatic Environment of Arg743
(A) Side view of the flip/R LBD colored by solvent-accessible surface area. Accessible residues range from white (fully accessible) to gray; inaccessible positions are depicted in blue. Green spheres denote water molecules. The red asterisk marks Arg743 residues. The figure was generated with CCP4mg.
(B) Image depicting the solvent network (red spheres) bridging the Arg743 side chains.
(C) Surface views outlining the electrostatic environment of the R/G site. Counter-charges (E486, D490, T744) within a 6.5 Å radius of Nη743 are indicated. Top views of the flip/R (left) and flop/G LBD (right). Arg743 side chains (gray) were superimposed onto the flop/G LBD to illustrate the gap generated by editing to Gly; the black dot marks N744. Protomers were color coded—chain A, yellow; chain C, gray.
Panels (B) and (C) were drawn with PyMOL (DeLano, 2002).

The above figures are reprinted by permission from Cell Press: Neuron (2006, 51, 85-97) copyright 2006.

Figures were selected by the author.