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Ligand-induced dynamic changes in extended PDZ domains from NHERF1.

Bhattacharya S, Ju JH, Orlova N, Khajeh JA, Cowburn D, Bu Z
J Mol Biol 425 2509-28 (2013)
Related entries: 2m0t, 2m0u

Cited: 22 times
EuropePMC logo PMID: 23583913

Abstract

The multi-domain scaffolding protein NHERF1 modulates the assembly and intracellular trafficking of various transmembrane receptors and ion-transport proteins. The two PDZ (postsynaptic density 95/disk large/zonula occluden 1) domains of NHERF1 possess very different ligand-binding capabilities: PDZ1 recognizes a variety of membrane proteins with high affinity, while PDZ2 only binds limited number of target proteins. Here using NMR, we have determined the structural and dynamic mechanisms that differentiate the binding affinities of the two PDZ domains, for the type 1 PDZ-binding motif (QDTRL) in the carboxyl terminus of cystic fibrosis transmembrane regulator. Similar to PDZ2, we have identified a helix-loop-helix subdomain coupled to the canonical PDZ1 domain. The extended PDZ1 domain is highly flexible with correlated backbone motions on fast and slow timescales, while the extended PDZ2 domain is relatively rigid. The malleability of the extended PDZ1 structure facilitates the transmission of conformational changes at the ligand-binding site to the remote helix-loop-helix extension. By contrast, ligand binding has only modest effects on the conformation and dynamics of the extended PDZ2 domain. The study shows that ligand-induced structural and dynamic changes coupled with sequence variation at the putative PDZ binding site dictate ligand selectivity and binding affinity of the two PDZ domains of NHERF1.

Articles - 2m0v mentioned but not cited (2)

  1. Ligand-induced dynamic changes in extended PDZ domains from NHERF1. Bhattacharya S, Ju JH, Orlova N, Khajeh JA, Cowburn D, Bu Z. J Mol Biol 425 2509-2528 (2013)
  2. The dipeptidyl peptidase IV inhibitors vildagliptin and K-579 inhibit a phospholipase C: a case of promiscuous scaffolds in proteins. Chakraborty S, Rendón-Ramírez A, Ásgeirsson B, Dutta M, Ghosh AS, Oda M, Venkatramani R, Rao BJ, Dandekar AM, Goñi FM. F1000Res 2 286 (2013)


Reviews citing this publication (5)

  1. Structures and target recognition modes of PDZ domains: recurring themes and emerging pictures. Ye F, Zhang M. Biochem. J. 455 1-14 (2013)
  2. Mechanistic basis of MAGUK-organized complexes in synaptic development and signalling. Zhu J, Shang Y, Zhang M. Nat. Rev. Neurosci. 17 209-223 (2016)
  3. Structure function relations in PDZ-domain-containing proteins: Implications for protein networks in cellular signalling. Manjunath GP, Ramanujam PL, Galande S. J. Biosci. 43 155-171 (2018)
  4. Recent Strategic Advances in CFTR Drug Discovery: An Overview. Rusnati M, D'Ursi P, Pedemonte N, Urbinati C, Ford RC, Cichero E, Uggeri M, Orro A, Fossa P. Int J Mol Sci 21 (2020)
  5. Noncanonical Sequences Involving NHERF1 Interaction with NPT2A Govern Hormone-Regulated Phosphate Transport: Binding Outside the Box. Mamonova T, Friedman PA. Int J Mol Sci 22 (2021)

Articles citing this publication (15)

  1. Protein interacting with C-kinase 1 (PICK1) binding promiscuity relies on unconventional PSD-95/discs-large/ZO-1 homology (PDZ) binding modes for nonclass II PDZ ligands. Erlendsson S, Rathje M, Heidarsson PO, Poulsen FM, Madsen KL, Teilum K, Gether U. J. Biol. Chem. 289 25327-25340 (2014)
  2. The tails of apical scaffolding proteins EBP50 and E3KARP regulate their localization and dynamics. Garbett D, Sauvanet C, Viswanatha R, Bretscher A. Mol. Biol. Cell 24 3381-3392 (2013)
  3. Phosphatidylinositol 4,5-bisphosphate clusters the cell adhesion molecule CD44 and assembles a specific CD44-Ezrin heterocomplex, as revealed by small angle neutron scattering. Chen X, Khajeh JA, Ju JH, Gupta YK, Stanley CB, Do C, Heller WT, Aggarwal AK, Callaway DJ, Bu Z. J. Biol. Chem. 290 6639-6652 (2015)
  4. Structural insights into neutrophilic migration revealed by the crystal structure of the chemokine receptor CXCR2 in complex with the first PDZ domain of NHERF1. Lu G, Wu Y, Jiang Y, Wang S, Hou Y, Guan X, Brunzelle J, Sirinupong N, Sheng S, Li C, Yang Z. PLoS ONE 8 e76219 (2013)
  5. Small molecule inhibition of the Na(+)/H(+) exchange regulatory factor 1 and parathyroid hormone 1 receptor interaction. Fitzpatrick JM, Pellegrini M, Cushing PR, Mierke DF. Biochemistry 53 5916-5922 (2014)
  6. Canonical and Noncanonical Sites Determine NPT2A Binding Selectivity to NHERF1 PDZ1. Mamonova T, Zhang Q, Khajeh JA, Bu Z, Bisello A, Friedman PA. PLoS ONE 10 e0129554 (2015)
  7. Nanoscale protein domain motion and long-range allostery in signaling proteins- a view from neutron spin echo sprectroscopy. Callaway DJ, Bu Z. Biophys Rev 7 165-174 (2015)
  8. A sequence upstream of canonical PDZ-binding motif within CFTR COOH-terminus enhances NHERF1 interaction. Sharma N, LaRusch J, Sosnay PR, Gottschalk LB, Lopez AP, Pellicore MJ, Evans T, Davis E, Atalar M, Na CH, Rosson GD, Belchis D, Milewski M, Pandey A, Cutting GR. Am. J. Physiol. Lung Cell Mol. Physiol. 311 L1170-L1182 (2016)
  9. Controllable Activation of Nanoscale Dynamics in a Disordered Protein Alters Binding Kinetics. Callaway DJE, Matsui T, Weiss T, Stingaciu LR, Stanley CB, Heller WT, Bu Z. J. Mol. Biol. 429 987-998 (2017)
  10. Dynamic structure of the full-length scaffolding protein NHERF1 influences signaling complex assembly. Bhattacharya S, Stanley CB, Heller WT, Friedman PA, Bu Z. J Biol Chem 294 11297-11310 (2019)
  11. In vivo crystals reveal critical features of the interaction between cystic fibrosis transmembrane conductance regulator (CFTR) and the PDZ2 domain of Na+/H+ exchange cofactor NHERF1. Martin ER, Barbieri A, Ford RC, Robinson RC. J Biol Chem 295 4464-4476 (2020)
  12. Multisite NHERF1 phosphorylation controls GRK6A regulation of hormone-sensitive phosphate transport. Vistrup-Parry M, Sneddon WB, Bach S, Strømgaard K, Friedman PA, Mamonova T. J Biol Chem 296 100473 (2021)
  13. An ensemble of cadherin-catenin-vinculin complex employs vinculin as the major F-actin binding mode. Shi B, Matsui T, Qian S, Weiss TM, Nicholl ID, Callaway DJE, Bu Z. Biophys J 122 2456-2474 (2023)
  14. Different conformational dynamics of PDZ1 and PDZ2 in full-length EBP50 analyzed by hydrogen/deuterium exchange mass spectrometry. Park JY, Duc NM, Kim DK, Lee SY, Li S, Seo MD, Woods VL, Chung KY. Biochem. Cell Biol. 93 290-297 (2015)
  15. On the analysis and comparison of conformer-specific essential dynamics upon ligand binding to a protein. Grosso M, Kalstein A, Parisi G, Roitberg AE, Fernandez-Alberti S. J Chem Phys 142 245101 (2015)


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