3QE1

Crystal Structure of PDZ domain of sorting nexin 27 (SNX27) fused to the C-terminal residues (ESESKV) of GIRK3

Summary for 3QE1

• Entry DOI: 10.2210/pdb3qe1/pdb
• Related: 3QDO 3QGL
• Descriptor: Sorting nexin-27, G protein-activated inward rectifier potassium channel 3 chimera (2 entities in total)
• Functional Keywords: pdz domain, pdz binding, girk3 regulation, early endosomes, brain, neurons, protein binding
• Biological source: Rattus norvegicus (rat); More
• Cellular location: Membrane; Multi-pass membrane protein: Q63511
• Total number of polymer chains: 1
• Total formula weight: 11230.65

Authors

Balana, B.,Kwiatkowski, W.,Choe, S. (deposition date: 2011-01-19, release date: 2011-03-16, Last modification date: 2023-09-13)

Primary citation

Balana, B.,Maslennikov, I.,Kwiatkowski, W.,Stern, K.M.,Bahima, L.,Choe, S.,Slesinger, P.A.
Mechanism underlying selective regulation of G protein-gated inwardly rectifying potassium channels by the psychostimulant-sensitive sorting nexin 27.
Proc.Natl.Acad.Sci.USA, 108:5831-5836, 2011

PubMed Abstract: G protein-gated inwardly rectifying potassium (GIRK) channels are important gatekeepers of neuronal excitability. The surface expression of neuronal GIRK channels is regulated by the psychostimulant-sensitive sorting nexin 27 (SNX27) protein through a class I (-X-Ser/Thr-X-Φ, where X is any residue and Φ is a hydrophobic amino acid) PDZ-binding interaction. The G protein-insensitive inward rectifier channel (IRK1) contains the same class I PDZ-binding motif but associates with a different synaptic PDZ protein, postsynaptic density protein 95 (PSD95). The mechanism by which SNX27 and PSD95 discriminate these channels was previously unclear. Using high-resolution structures coupled with biochemical and functional analyses, we identified key amino acids upstream of the channel's canonical PDZ-binding motif that associate electrostatically with a unique structural pocket in the SNX27-PDZ domain. Changing specific charged residues in the channel's carboxyl terminus or in the PDZ domain converts the selective association and functional regulation by SNX27. Elucidation of this unique interaction site between ion channels and PDZ-containing proteins could provide a therapeutic target for treating brain diseases.

PubMed: 21422294
DOI: 10.1073/pnas.1018645108

Experimental method

X-RAY DIFFRACTION (1.68 Å)