5b64

A novel binding mode of MAGUK GK domain revealed by DLG GK domain in complex with KIF13B MBS domainA novel binding mode of MAGUK GK domain revealed by DLG GK domain in complex with KIF13B MBS domain

Structural highlights

5b64 is a 2 chain structure with sequence from Mus musculus and Rattus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DLG4_RAT Interacts with the cytoplasmic tail of NMDA receptor subunits and shaker-type potassium channels. Required for synaptic plasticity associated with NMDA receptor signaling. Overexpression or depletion of DLG4 changes the ratio of excitatory to inhibitory synapses in hippocampal neurons. May reduce the amplitude of ASIC3 acid-evoked currents by retaining the channel intracellularly. May regulate the intracellular trafficking of ADR1B.^[1] ^[2]

Publication Abstract from PubMed

The membrane-associated guanylate kinase (MAGUK) scaffold proteins share a signature guanylate kinase (GK) domain. Despite their diverse functional roles in cell polarity control and synaptic signaling, the currently known mode of action of MAGUK GK is via its binding to phosphorylated short peptides from target proteins. Here, we discover that the GK domain of DLG MAGUK binds to an unphosphorylated and autonomously folded domain within the stalk region (MAGUK binding stalk [MBS] domain) of a kinesin motor KIF13B with high specificity and affinity. The structure of DLG4 GK in complex with KIF13B MBS reveals the molecular mechanism governing this atypical GK/target recognition mode and provides insights into DLG/KIF13B complex-mediated regulation of diverse cellular processes such as asymmetric cell division. We further show that binding to non-phosphorylated targets is another general property of MAGUK GKs, thus expanding the mechanisms of action of the MAGUK family proteins.

An Atypical MAGUK GK Target Recognition Mode Revealed by the Interaction between DLG and KIF13B.,Zhu J, Shang Y, Xia Y, Zhang R, Zhang M Structure. 2016 Sep 15. pii: S0969-2126(16)30241-6. doi:, 10.1016/j.str.2016.08.008. PMID:27642159^[3]

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

References

↑ Hruska-Hageman AM, Benson CJ, Leonard AS, Price MP, Welsh MJ. PSD-95 and Lin-7b interact with acid-sensing ion channel-3 and have opposite effects on H+- gated current. J Biol Chem. 2004 Nov 5;279(45):46962-8. Epub 2004 Aug 17. PMID:15317815 doi:10.1074/jbc.M405874200
↑ Prange O, Wong TP, Gerrow K, Wang YT, El-Husseini A. A balance between excitatory and inhibitory synapses is controlled by PSD-95 and neuroligin. Proc Natl Acad Sci U S A. 2004 Sep 21;101(38):13915-20. Epub 2004 Sep 9. PMID:15358863 doi:10.1073/pnas.0405939101
↑ Zhu J, Shang Y, Xia Y, Zhang R, Zhang M. An Atypical MAGUK GK Target Recognition Mode Revealed by the Interaction between DLG and KIF13B. Structure. 2016 Sep 15. pii: S0969-2126(16)30241-6. doi:, 10.1016/j.str.2016.08.008. PMID:27642159 doi:http://dx.doi.org/10.1016/j.str.2016.08.008

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OCA

[1] Hruska-Hageman AM, Benson CJ, Leonard AS, Price MP, Welsh MJ. PSD-95 and Lin-7b interact with acid-sensing ion channel-3 and have opposite effects on H+- gated current. J Biol Chem. 2004 Nov 5;279(45):46962-8. Epub 2004 Aug 17. PMID:15317815 doi:10.1074/jbc.M405874200

[2] Prange O, Wong TP, Gerrow K, Wang YT, El-Husseini A. A balance between excitatory and inhibitory synapses is controlled by PSD-95 and neuroligin. Proc Natl Acad Sci U S A. 2004 Sep 21;101(38):13915-20. Epub 2004 Sep 9. PMID:15358863 doi:10.1073/pnas.0405939101

[3] Zhu J, Shang Y, Xia Y, Zhang R, Zhang M. An Atypical MAGUK GK Target Recognition Mode Revealed by the Interaction between DLG and KIF13B. Structure. 2016 Sep 15. pii: S0969-2126(16)30241-6. doi:, 10.1016/j.str.2016.08.008. PMID:27642159 doi:http://dx.doi.org/10.1016/j.str.2016.08.008

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