Interdomain chaperoning between PSD-95, Dlg, and Zo-1 (PDZ) domains of glutamate receptor-interacting proteins.
The multiple PSD-95, Dlg, and Zo-1 (PDZ) domain protein, glutamate receptor-interacting protein (GRIP), is involved in the clustering and trafficking of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor by directly binding to the cytoplasmic tail of the receptor's GluR2 subunit. Both the forth and fifth PDZ domains (PDZ4 and PDZ5) of GRIP are required for effective binding to the receptor. Using NMR and circular dichroism spectroscopic techniques, we show that PDZ5 is completely unstructured in solution. Freshly prepared PDZ4 is largely folded, but the domain can spontaneously unfold. Neither PDZ4 nor PDZ5 binds to GluR2 in solution. Unexpectedly, when PDZ4 and PDZ5 are covalently connected (i.e. PDZ45), both PDZ domains become well folded and stable in solution. The covalent linkage of the two PDZ domains is essential for proper folding of the tandem PDZ domains and its effective binding to GluR2. The interdomain chaperoning effect observed in the PDZ domains of GRIP represents a previously uncharacterized function of PDZ domains.
Zhang
Q
Q
Department of Biochemistry, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, People's Republic of China.
Fan
J S
JS
Zhang
M
M
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002850:Chromatography, Gel; D002942:Circular Dichroism; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D019281:Dimerization; D000074288:Discs Large Homolog 1 Protein; D000076122:Disks Large Homolog 4 Protein; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009682:Magnetic Resonance Spectroscopy; D008565:Membrane Proteins / Q000737:chemistry*; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D051381:Rats; D017470:Receptors, Glutamate / Q000737:chemistry*; D062826:Zonula Occludens-1 Protein
D048868:Adaptor Proteins, Signal Transducing; C513314:DLG1 protein, human; D000074288:Discs Large Homolog 1 Protein; D000076122:Disks Large Homolog 4 Protein; C501119:Dlg1 protein, rat; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D011506:Proteins; D017470:Receptors, Glutamate; C569042:TJP1 protein, human; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; C033652:postsynaptic density proteins