3GJ9

crystal structure of TIP-1 in complex with c-terminal of Kir2.3

Summary for 3GJ9

• Entry DOI: 10.2210/pdb3gj9/pdb
• Related: 3diw 3dj1 3dj3
• Descriptor: Tax1-binding protein 3, C-terminal peptide from Inward rectifier potassium channel 4, ZINC ION, ... (5 entities in total)
• Functional Keywords: tip-1, kir2.3, pdz domain, cytoplasm, nucleus, phosphoprotein, wnt signaling pathway, signaling protein
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: O14907; Membrane; Multi-pass membrane protein: P48050
• Total number of polymer chains: 4
• Total formula weight: 30327.50

Authors

Shen, Y. (deposition date: 2009-03-08, release date: 2009-12-15, Last modification date: 2023-11-01)

Primary citation

Yan, X.,Zhou, H.,Zhang, J.,Shi, C.,Xie, X.,Wu, Y.,Tian, C.,Shen, Y.,Long, J.
Molecular mechanism of inward rectifier potassium channel 2.3 regulation by tax-interacting protein-1
J.Mol.Biol., 392:967-976, 2009

PubMed Abstract: Inwardly rectifying potassium channel 2.3 (Kir2.3) is specifically targeted on the basolateral membranes of epithelial and neuronal cells, and it thus plays an important role in maintaining potassium homeostasis. Tax-interacting protein-1 (TIP-1), an atypical PDZ-domain-containing protein, binds to Kir2.3 with a high affinity, causing the intracellular accumulation of Kir2.3 in cultured epithelial cells. However, the molecular basis of the TIP-1/Kir2.3 interaction is still poorly understood. Here, we present the crystal structure of TIP-1 in complex with the C-terminal Kir2.3-peptide (residues 436-445) to reveal the molecular details of the interaction between them. Moreover, isothermal titration calorimetry experiments show that the C-terminal Kir2.3-peptide binds much more strongly to TIP-1 than to mammalian Lin-7, indicating that TIP-1 can compete with mammalian Lin-7 to uncouple Kir2.3 from its basolateral membrane anchoring complex. We further show that the phosphorylation/dephosphorylation of Ser443 within the C-terminal Kir2.3 PDZ-binding motif RRESAI dynamically regulates the Kir2.3/TIP-1 association in heterologous HEK293T cells. These data suggest that TIP-1 may act as an important regulator for the endocytic pathway of Kir2.3.

PubMed: 19635485
DOI: 10.1016/j.jmb.2009.07.060

Experimental method

X-RAY DIFFRACTION (2.8 Å)