A Systematic Family-wide Investigation Reveals That ~30% of Mammalian PDZ Domains Engage in PDZ-PDZ Interactions

Overview

Journal Chem Biol

Publisher Elsevier

Specialties Biochemistry
Biology
Chemistry

Date 2011 Sep 28

PMID 21944753

Citations 28

Authors

Bryan H Chang

Taranjit S Gujral

Ethan S Karp

Raghida Bukhalid

Viara P Grantcharova

Gavin MacBeath

Affiliations

Soon will be listed here.

Abstract

PDZ domains are independently folded modules that typically mediate protein-protein interactions by binding to the C termini of their target proteins. However, in a few instances, PDZ domains have been reported to dimerize with other PDZ domains. To investigate this noncanonical-binding mode further, we used protein microarrays comprising virtually every mouse PDZ domain to systematically query all possible PDZ-PDZ pairs. We then used fluorescence polarization to retest and quantify interactions and coaffinity purification to test biophysically validated interactions in the context of their full-length proteins. Overall, we discovered 37 PDZ-PDZ interactions involving 46 PDZ domains (~30% of all PDZ domains tested), revealing that dimerization is a more frequently used binding mode than was previously appreciated. This suggests that many PDZ domains evolved to form multiprotein complexes by simultaneously interacting with more than one ligand.

Citing Articles

Engineering paralog-specific PSD-95 recombinant binders as minimally interfering multimodal probes for advanced imaging techniques.

Rimbault C, Breillat C, Compans B, Toulme E, Vicente F, Fernandez-Monreal M Elife. 2024; 13.

PMID: 38167295 PMC: 10803022. DOI: 10.7554/eLife.69620.

Microtubule-Associated Serine/Threonine (MAST) Kinases in Development and Disease.

Rumpf M, Pautz S, Drebes B, Herberg F, Muller H Int J Mol Sci. 2023; 24(15).

PMID: 37569286 PMC: 10419289. DOI: 10.3390/ijms241511913.

A Significant Difference in Core PDZ Interactivity of SARS-CoV, SARS-CoV2 and MERS-CoV Protein E Peptide PDZ Motifs In Vitro.

Baliova M, Jahodova I, Jursky F Protein J. 2023; 42(4):253-262.

PMID: 36932261 PMC: 10023026. DOI: 10.1007/s10930-023-10103-x.

Peptide Targeting of PDZ-Dependent Interactions as Pharmacological Intervention in Immune-Related Diseases.

Gutierrez-Gonzalez L, Rivas-Fuentes S, Guzman-Beltran S, Flores-Flores A, Rosas-Garcia J, Santos-Mendoza T Molecules. 2021; 26(21).

PMID: 34770776 PMC: 8588348. DOI: 10.3390/molecules26216367.

PDZ Sample Quality Assessment by Biochemical and Biophysical Characterizations.

Caillet-Saguy C, Brule S, Wolff N, Raynal B Methods Mol Biol. 2021; 2256:89-124.

PMID: 34014518 DOI: 10.1007/978-1-0716-1166-1_6.

References

Xu X, Choudhury A, Li X, Montell C . Coordination of an array of signaling proteins through homo- and heteromeric interactions between PDZ domains and target proteins. J Cell Biol. 1998; 142(2):545-55. PMC: 2133053. DOI: 10.1083/jcb.142.2.545. View

Brenman J, Christopherson K, Craven S, McGee A, Bredt D . Cloning and characterization of postsynaptic density 93, a nitric oxide synthase interacting protein. J Neurosci. 1996; 16(23):7407-15. PMC: 6579097. View

Doyle D, Lee A, Lewis J, Kim E, Sheng M, Mackinnon R . Crystal structures of a complexed and peptide-free membrane protein-binding domain: molecular basis of peptide recognition by PDZ. Cell. 1996; 85(7):1067-76. DOI: 10.1016/s0092-8674(00)81307-0. View

Cho K, Hunt C, Kennedy M . The rat brain postsynaptic density fraction contains a homolog of the Drosophila discs-large tumor suppressor protein. Neuron. 1992; 9(5):929-42. DOI: 10.1016/0896-6273(92)90245-9. View

Stiffler M, Chen J, Grantcharova V, Lei Y, Fuchs D, Allen J . PDZ domain binding selectivity is optimized across the mouse proteome. Science. 2007; 317(5836):364-9. PMC: 2674608. DOI: 10.1126/science.1144592. View

Bilder D . PDZ proteins and polarity: functions from the fly. Trends Genet. 2001; 17(9):511-9. DOI: 10.1016/s0168-9525(01)02407-6. View

Harris B, Lim W . Mechanism and role of PDZ domains in signaling complex assembly. J Cell Sci. 2001; 114(Pt 18):3219-31. DOI: 10.1242/jcs.114.18.3219. View

MASUKO N, Makino K, Kuwahara H, Fukunaga K, Sudo T, Araki N . Interaction of NE-dlg/SAP102, a neuronal and endocrine tissue-specific membrane-associated guanylate kinase protein, with calmodulin and PSD-95/SAP90. A possible regulatory role in molecular clustering at synaptic sites. J Biol Chem. 1999; 274(9):5782-90. DOI: 10.1074/jbc.274.9.5782. View

Sheng M, Sala C . PDZ domains and the organization of supramolecular complexes. Annu Rev Neurosci. 2001; 24:1-29. DOI: 10.1146/annurev.neuro.24.1.1. View

10.

Woods D, Bryant P . ZO-1, DlgA and PSD-95/SAP90: homologous proteins in tight, septate and synaptic cell junctions. Mech Dev. 1993; 44(2-3):85-9. DOI: 10.1016/0925-4773(93)90059-7. View

11.

Chen J, Chang B, Allen J, Stiffler M, MacBeath G . Predicting PDZ domain-peptide interactions from primary sequences. Nat Biotechnol. 2008; 26(9):1041-5. PMC: 2655215. DOI: 10.1038/nbt.1489. View

12.

Yan Y, Marriott G . Analysis of protein interactions using fluorescence technologies. Curr Opin Chem Biol. 2003; 7(5):635-40. DOI: 10.1016/j.cbpa.2003.08.017. View

13.

Brenman J, Chao D, Gee S, McGee A, Craven S, Santillano D . Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alpha1-syntrophin mediated by PDZ domains. Cell. 1996; 84(5):757-67. DOI: 10.1016/s0092-8674(00)81053-3. View

14.

Harris B, Hillier B, Lim W . Energetic determinants of internal motif recognition by PDZ domains. Biochemistry. 2001; 40(20):5921-30. DOI: 10.1021/bi010142l. View

15.

Tochio H, Mok Y, Zhang Q, Kan H, Bredt D, Zhang M . Formation of nNOS/PSD-95 PDZ dimer requires a preformed beta-finger structure from the nNOS PDZ domain. J Mol Biol. 2000; 303(3):359-70. DOI: 10.1006/jmbi.2000.4148. View

16.

Stiffler M, Grantcharova V, Sevecka M, MacBeath G . Uncovering quantitative protein interaction networks for mouse PDZ domains using protein microarrays. J Am Chem Soc. 2006; 128(17):5913-22. PMC: 2533859. DOI: 10.1021/ja060943h. View

17.

Kamberov E, Makarova O, Roh M, Liu A, Karnak D, Straight S . Molecular cloning and characterization of Pals, proteins associated with mLin-7. J Biol Chem. 2001; 275(15):11425-31. DOI: 10.1074/jbc.275.15.11425. View

18.

Garner C, Nash J, Huganir R . PDZ domains in synapse assembly and signalling. Trends Cell Biol. 2000; 10(7):274-80. DOI: 10.1016/s0962-8924(00)01783-9. View

19.

Jameson D, Seifried S . Quantification of protein-protein interactions using fluorescence polarization. Methods. 1999; 19(2):222-33. DOI: 10.1006/meth.1999.0853. View

20.

Songyang Z, Fanning A, Fu C, Xu J, Marfatia S, Chishti A . Recognition of unique carboxyl-terminal motifs by distinct PDZ domains. Science. 1997; 275(5296):73-7. DOI: 10.1126/science.275.5296.73. View