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5zds

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Crystal structure of the second PDZ domain of Frmpd2

Structural highlights

5zds is a 1 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.8Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

FRPD2_MOUSE Functions as a scaffold protein and likely plays a role in N-methyl-D-aspartic acid receptor (NMDAR)-mediated synaptic excitatory transmission (PubMed:31196628). May be involved in synapse formation in cone photoreceptor cells (PubMed:29590622). May play a role in the regulation of tight junction formation (By similarity). Binds phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) (By similarity). May pNF-kappa-Blay a role in the regulation of NOD2-mediated NF-kappa-B activation in immune response (By similarity).[UniProtKB:Q68DX3]^[1] ^[2]

Publication Abstract from PubMed

The scaffold proteins Frmpd2 is localized at the basolateral membranes of polarized epithelial cells and associated with tight junction formation. In this report, we found that the Frmpd2 is specifically expressed at postsynaptic membrane. By using of co-immunoprecipitation and GST pull-down, Frmpd2 was reported to interact with postsynaptic excitatory N-methyl-d-aspartic acid (NMDA) receptors in vivo and in vitro. In addition, we demonstrated that the second PDZ (PDZ2) domain but not the first or third PDZ domain of Frmpd2 binds to the C-terminus of GluN2A and GluN2B, two subunits of NMDA receptors. By surface plasmon resonance, the affinity of Frmpd2-isolated PDZ2 to GluN2A and GluN2B was identified, which indicates that the interaction of Frmpd2 to GluN2A subunit is more strongly than that to GluN2B subunit. The crystal structure of the PDZ2 domain of the mouse homologue of Frmpd2 was further solved. Some amino acid residues of the PDZ2 structure are supposed to associate with the GluN2A binding. Our study suggests that the scaffold protein Frmpd2 is probably involved in synaptic NMDA receptors-mediated neural excitatory and neurotoxicity in a PDZ2 domain-dependent manner.

The second PDZ domain of scaffold protein Frmpd2 binds to GluN2A of NMDA receptors.,Lu X, Zhang Q, Wang T Biochem Biophys Res Commun. 2019 Aug 13;516(1):63-67. doi: , 10.1016/j.bbrc.2019.05.087. Epub 2019 Jun 10. PMID:31196628^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ueno A, Omori Y, Sugita Y, Watanabe S, Chaya T, Kozuka T, Kon T, Yoshida S, Matsushita K, Kuwahara R, Kajimura N, Okada Y, Furukawa T. Lrit1, a Retinal Transmembrane Protein, Regulates Selective Synapse Formation in Cone Photoreceptor Cells and Visual Acuity. Cell Rep. 2018 Mar 27;22(13):3548-3561. PMID:29590622 doi:10.1016/j.celrep.2018.03.007
↑ Lu X, Zhang Q, Wang T. The second PDZ domain of scaffold protein Frmpd2 binds to GluN2A of NMDA receptors. Biochem Biophys Res Commun. 2019 Aug 13;516(1):63-67. PMID:31196628 doi:10.1016/j.bbrc.2019.05.087
↑ Lu X, Zhang Q, Wang T. The second PDZ domain of scaffold protein Frmpd2 binds to GluN2A of NMDA receptors. Biochem Biophys Res Commun. 2019 Aug 13;516(1):63-67. PMID:31196628 doi:10.1016/j.bbrc.2019.05.087