PDBsum entry: 1kjw

Neuropeptide

PDB id: 1kjw

Contents

Protein chain

292 a.a. *

Ligands

SO4 ×2

Waters ×126

* Residue conservation analysis

PDB id:

1kjw

Name:

Neuropeptide

Title:

Sh3-guanylate kinase module from psd-95

Structure:

Postsynaptic density protein 95. Chain: a. Fragment: sh3 domain/guanylate kinase domain. Synonym: psd-95, postsynaptic protein sap90, synapse- associated protein 90. Engineered: yes

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.80Å R-factor: 0.230 R-free: 0.250

Authors:

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

Key ref:

A.W.McGee et al. (2001). Structure of the SH3-guanylate kinase module from PSD-95 suggests a mechanism for regulated assembly of MAGUK scaffolding proteins. Mol Cell, 8, 1291-1301. PubMed id: 11779504 DOI: 10.1016/S1097-2765(01)00411-7

Date:

05-Dec-01 Release date: 09-Jan-02

Protein chain

P31016  (DLG4_RAT) -  Disks large homolog 4

Seq: 724 a.a.

Struc: 292 a.a.

DOI no: 10.1016/S1097-2765(01)00411-7

Mol Cell 8:1291-1301 (2001)

PubMed id: 11779504

Structure of the SH3-guanylate kinase module from PSD-95 suggests a mechanism for regulated assembly of MAGUK scaffolding proteins.

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

ABSTRACT

Membrane-associated guanylate kinases (MAGUKs), such as PSD-95, are modular scaffolds that organize signaling complexes at synapses and other cell junctions. MAGUKs contain PDZ domains, which recruit signaling proteins, as well as a Src homology 3 (SH3) and a guanylate kinase-like (GK) domain, implicated in scaffold oligomerization. The crystal structure of the SH3-GK module from PSD-95 reveals that these domains form an integrated unit: the SH3 fold comprises noncontiguous sequence elements divided by a hinge region and the GK domain. These elements compose two subdomains that can assemble in either an intra- or intermolecular fashion to complete the SH3 fold. We propose a model for MAGUK oligomerization in which complementary SH3 subdomains associate by 3D domain swapping. This model provides a possible mechanism for ligand regulation of oligomerization.

Selected figure(s)

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 reprinted by permission from Cell Press: Mol Cell (2001, 8, 1291-1301) copyright 2001.

Figures were selected by an automated process.