title: Structure of the SH3-guanylate kinase module from PSD-95 suggests a mechanism for regulated assembly of MAGUK scaffolding proteins.
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.
authors.affiliation: Department of Physiology, University of California-San Francisco, San Francisco, CA 94143, USA.
authors.forename: A W
authors.initials: AW
authors.lastname: McGee
authors.forename: S R
authors.initials: SR
authors.lastname: Dakoji
authors.forename: O
authors.initials: O
authors.lastname: Olsen
authors.forename: D S
authors.initials: DS
authors.lastname: Bredt
authors.forename: W A
authors.initials: WA
authors.lastname: Lim
authors.forename: K E
authors.initials: KE
authors.lastname: Prehoda
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001051:Apoenzymes / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D000076122:Disks Large Homolog 4 Protein; D006147:Guanine / Q000378:metabolism; D051528:Guanylate Kinases; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism*; D009703:Nucleoside-Phosphate Kinase / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D016415:Sequence Alignment; D018909:src Homology Domains
chemical_list: D001051:Apoenzymes; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins; C501451:Mpp2 protein, rat; D009419:Nerve Tissue Proteins; C033652:postsynaptic density proteins; D006147:Guanine; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases