PDBsum entry 2xkx

Structural protein

PDB id: 2xkx

Contents

Protein chains

721 a.a.*

* C-alpha coords only

References listed in PDB file

Key reference

Title

Self-Directed assembly and clustering of the cytoplasmic domains of inwardly rectifying kir2.1 potassium channels on association with psd-95.

Authors

S.Fomina, T.D.Howard, O.K.Sleator, M.Golovanova, L.O'Ryan, M.L.Leyland, J.G.Grossmann, R.F.Collins, S.M.Prince.

Ref.

Biochim Biophys Acta, 2011, 1808, 2374-2389.

PubMed id

21756874

Abstract

No abstract given.

Secondary reference #1

Title

Supramodular structure and synergistic target binding of the n-Terminal tandem pdz domains of psd-95.

Authors

J.F.Long, H.Tochio, P.Wang, J.S.Fan, C.Sala, M.Niethammer, M.Sheng, M.Zhang.

Ref.

J Mol Biol, 2003, 327, 203-214. [DOI no: 10.1016/S0022-2836(03)00113-X]

PubMed id

12614619

Figure 1.
Figure 1. Structure of PSD-95 PDZ1 determined by NMR spectroscopy. (A) Stereoview showing the best-fit superposition of the backbone atoms (N, C^a, and C') of the final 20 structures of PSD-95 PDZ1. The structures are superimposed against the average structure using the residues 64-148. The structural statistics are summarized in Table 1. (B) Ribbon diagram presentation of PSD-95 PDZ1. The secondary structure elements are labelled following the scheme used in the crystal structure of PSD-95 PDZ3. [7] (C) Comparison of the 3D structures of PDZ1 and PDZ2 of PSD-95. The backbone traces (N, C^a, and C') of PDZ1 (gold) and PDZ2 (yellow) are superimposed. The two structures were fit to each other by excluding the GLGF-loop, bB/bC loop and the two termini. The rmsd between the backbones of the two PDZ domains is 1.35 Å.

Figure 5.
Figure 5. Functional role of conformation-restrained tandem PDZ repeats in PSD-95. (A) Extending the PDZ12 linker by introducing flexible amino acid residues reduces the size of the Kv1.4 channel clusters mediated by N-PDZ12. Myc-tagged constructs N-PDZ1-2 wild-type (N-PDZ12), the deletion mutant of N-PDZ12 (N-PDZ12Del) and the insertion mutant of N-PDZ12 (N-PDZ1-2Ins) were co-transfected in COS7 cells with potassium channel subunit Kv1.4. Cells cotransfected with different constructs, as indicated, were fixed two days after transfection and stained with Kv1.4 antibodies to visualize the potassium channel clusters. The schematics of the deletions and insertion mutations used in this study are shown. Insets show higher-magnification views of Kv1.4 clusters. (B) Frequency distribution (left) and mean values (right) of Kv1.4 cluster areas mediated by N-PDZ12, N-PDZ12(Del) and N-PDZ12(Ins), measured from at least ten cells for each construct. The scale bars represent 5 µm or 15 µm for the insets. An asterisk (*) indicates significance at p <0.01 in an unpaired, two-tailed Student's t-test.

The above figures are reproduced from the cited reference with permission from Elsevier

Secondary reference #2

Title

Solution structure and backbone dynamics of the second pdz domain of postsynaptic density-95.

Authors

H.Tochio, F.Hung, M.Li, D.S.Bredt, M.Zhang.

Ref.

J Mol Biol, 2000, 295, 225-237. [DOI no: 10.1006/jmbi.1999.3350]

PubMed id

10623522

Figure 2.
Figure 2. Stereoview showing the best-fit superposition of the backbone atoms (N, C a , and C0) of the final 20 struc- tures of PSD-95 PDZ2. The structures are superimposed against the average structure using the residues 158-246. The program MOLMOL (Koradi et al., 1996) was used to generate the Figure.

Figure 6.
Figure 6. Model of the PSD-95 PDZ2 and the nNOS PDZ complex. In this model, PSD-95 PDZ2 (green) is superimposed on the a1- syntrophin PDZ domain (red) (Hillier et al., 1999). The nNOS PDZ domain is shown in blue. The Figure was generated using MOL- SCRIPT and Raster3D.

The above figures are reproduced from the cited reference with permission from Elsevier

Secondary reference #3

Title

Structure of the third pdz domain of psd-95 protein complexed with kketwv peptide ligand

Authors

D.Saro, Z.Wawrzak, P.Martin, J.Vickrey, A.Paredes, L.Kovarm.Spaller.

Ref.

TO BE PUBLISHED ...

Secondary reference #4

Title

Structure of the sh3-Guanylate kinase module from psd-95 suggests a mechanism for regulated assembly of maguk scaffolding proteins.

Authors

A.W.Mcgee, S.R.Dakoji, O.Olsen, D.S.Bredt, W.A.Lim, K.E.Prehoda.

Ref.

Mol Cell, 2001, 8, 1291-1301. [DOI no: 10.1016/S1097-2765(01)00411-7]

PubMed id

11779504

Figure 4.
Figure 4. Comparison of the PSD-95 Split SH3 Structure with Canonical SH3 Domain Structure(A) Stereo ribbon diagrams of the PSD-95 SH3 fold (upper), including the intervening hinge region and the additional β strand F, and the C-terminal SH3 domain of SEM-5 (lower) complexed with a peptide ligand (Lim et al., 1994b). In PSD-95, a tyrosine (523) from the separated E β strand packs into the hydrophobic core of the SH3 fold, in place of a valine normally observed in canonical SH3 domains (Val 208 in SEM-5). The position of the 3[10] helix in SEM-5 is indicated. The β strands for PSD-95 and SEM-5 are labeled A–F and A–E, respectively.(B) Secondary structure diagrams of PSD-95 and SEM-5 reveal the conserved overall topology. The hinge region in PSD-95, which separates β strands D and E, occludes the canonical peptide binding surface. The GK domain is inserted between β strands E and F. The positions of the various loops and the conserved segment of 3[10] helix are shown in SEM-5.(C) Schematic comparison of the peptide ligand binding surfaces for PSD-95 and SEM-5. Aromatic side chains critical for ligand recognition are represented as planar projections. PSD-95 lacks the central conserved tyrosine residue. A docked polyproline II (PPII) helical ligand is shown for the canonical SH3 domain.

Figure 6.
Figure 6. The Hinge Region Is Variable and Can Modulate Inter- Versus Intramolecular SH3 Assembly(A) Schematic representations of intramolecular SH3 assembly (upper), a 3D domain swapped open oligomeric chain (left), and a closed dimer (right).(B) Alignment of the PSD-95 SH3 fold (red) with the structures of eight canonical SH3 domains (black) shows that the hinge insert replaces a conserved segment of 3[10] helix (bold).(C) The hinge region is variable in length and is the site of protein binding and alternative splicing. Calmodulin and protein 4.1 bind some MAGUKs within the hinge region. Two mutations in Drosophila DLG that are capable of interallelic complementation are indicated with arrows.(D) Schematic representations of the SH3-GK mutant proteins used to probe the role of the hinge region in SH3 3D-domain swapped assembly.(E) Elution profiles for the proteins diagrammed in (D). Unlike the wt and other mutants, the Pro[5]-Δhinge protein elutes with a significant peak corresponding to the dimer species.

The above figures are reproduced from the cited reference with permission from Cell Press