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Conformation changes, N-terminal involvement, and cGMP signal relay in the phosphodiesterase-5 GAF domain.

Wang H, Robinson H, Ke H
J Biol Chem 285 38149-56 (2010)
Cited: 24 times
EuropePMC logo PMID: 20861010

Abstract

The activity of phosphodiesterase-5 (PDE5) is specific for cGMP and is regulated by cGMP binding to GAF-A in its regulatory domain. To better understand the regulatory mechanism, x-ray crystallographic and biochemical studies were performed on constructs of human PDE5A1 containing the N-terminal phosphorylation segment, GAF-A, and GAF-B. Superposition of this unliganded GAF-A with the previously reported NMR structure of cGMP-bound PDE5 revealed dramatic conformational differences and suggested that helix H4 and strand B3 probably serve as two lids to gate the cGMP-binding pocket in GAF-A. The structure also identified an interfacial region among GAF-A, GAF-B, and the N-terminal loop, which may serve as a relay of the cGMP signal from GAF-A to GAF-B. N-terminal loop 98-147 was physically associated with GAF-B domains of the dimer. Biochemical analyses showed an inhibitory effect of this loop on cGMP binding and its involvement in the cGMP-induced conformation changes.

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  1. Biosynthesis of the Pseudomonas aeruginosa Extracellular Polysaccharides, Alginate, Pel, and Psl. Franklin MJ, Nivens DE, Weadge JT, Howell PL. Front Microbiol 2 167 (2011)
  2. Structure of the cytoplasmic region of PelD, a degenerate diguanylate cyclase receptor that regulates exopolysaccharide production in Pseudomonas aeruginosa. Whitney JC, Colvin KM, Marmont LS, Robinson H, Parsek MR, Howell PL. J Biol Chem 287 23582-23593 (2012)
  3. Conformation changes, N-terminal involvement, and cGMP signal relay in the phosphodiesterase-5 GAF domain. Wang H, Robinson H, Ke H. J Biol Chem 285 38149-38156 (2010)
  4. Structures of the PelD cyclic diguanylate effector involved in pellicle formation in Pseudomonas aeruginosa PAO1. Li Z, Chen JH, Hao Y, Nair SK. J Biol Chem 287 30191-30204 (2012)
  5. Identification of amino acid residues responsible for the selectivity of tadalafil binding to two closely related phosphodiesterases, PDE5 and PDE6. Cahill KB, Quade JH, Carleton KL, Cote RH. J Biol Chem 287 41406-41416 (2012)
  6. The Molecular Organization of Human cGMP Specific Phosphodiesterase 6 (PDE6): Structural Implications of Somatic Mutations in Cancer and Retinitis Pigmentosa. Maryam A, Vedithi SC, Khalid RR, Alsulami AF, Torres PHM, Siddiqi AR, Blundell TL. Comput Struct Biotechnol J 17 378-389 (2019)
  7. A general method for directly phasing diffraction data from high-solvent-content protein crystals. Kingston RL, Millane RP. IUCrJ 9 648-665 (2022)
  8. Development of a red fluorescent protein-based cGMP indicator applicable for live-cell imaging. Takizawa M, Osuga Y, Ishida R, Mita M, Harada K, Ueda H, Kitaguchi T, Tsuboi T. Commun Biol 5 833 (2022)


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  1. Advances in targeting cyclic nucleotide phosphodiesterases. Maurice DH, Ke H, Ahmad F, Wang Y, Chung J, Manganiello VC. Nat Rev Drug Discov 13 290-314 (2014)
  2. Mammalian cyclic nucleotide phosphodiesterases: molecular mechanisms and physiological functions. Francis SH, Blount MA, Corbin JD. Physiol Rev 91 651-690 (2011)
  3. Cyclic nucleotide phosphodiesterase (PDE) isozymes as targets of the intracellular signalling network: benefits of PDE inhibitors in various diseases and perspectives for future therapeutic developments. Keravis T, Lugnier C. Br J Pharmacol 165 1288-1305 (2012)
  4. Phosphodiesterases and cyclic GMP regulation in heart muscle. Lee DI, Kass DA. Physiology (Bethesda) 27 248-258 (2012)
  5. Role of sGC-dependent NO signalling and myocardial infarction risk. Wobst J, Kessler T, Dang TA, Erdmann J, Schunkert H. J Mol Med (Berl) 93 383-394 (2015)
  6. Photoreceptor phosphodiesterase (PDE6): activation and inactivation mechanisms during visual transduction in rods and cones. Cote RH. Pflugers Arch 473 1377-1391 (2021)

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  2. Longin and GAF domains: structural evolution and adaptation to the subcellular trafficking machinery. De Franceschi N, Wild K, Schlacht A, Dacks JB, Sinning I, Filippini F. Traffic 15 104-121 (2014)
  3. Cryo-EM structure of phosphodiesterase 6 reveals insights into the allosteric regulation of type I phosphodiesterases. Gulati S, Palczewski K, Engel A, Stahlberg H, Kovacik L. Sci Adv 5 eaav4322 (2019)
  4. Survey of phosphorylation near drug binding sites in the Protein Data Bank (PDB) and their effects. Smith KP, Gifford KM, Waitzman JS, Rice SE. Proteins 83 25-36 (2015)
  5. Structural basis of molecular logic OR in a dual-sensor histidine kinase. Shin H, Ren Z, Zeng X, Bandara S, Yang X. Proc Natl Acad Sci U S A 116 19973-19982 (2019)
  6. Distinct patterns of compartmentalization and proteolytic stability of PDE6C mutants linked to achromatopsia. Cheguru P, Majumder A, Artemyev NO. Mol Cell Neurosci 64 1-8 (2015)
  7. Allosteric Regulation of Rod Photoreceptor Phosphodiesterase 6 (PDE6) Elucidated by Chemical Cross-Linking and Quantitative Mass Spectrometry. Chu F, Hogan D, Gupta R, Gao XZ, Nguyen HT, Cote RH. J Mol Biol 431 3677-3689 (2019)
  8. Cyclic nucleotide binding and structural changes in the isolated GAF domain of Anabaena adenylyl cyclase, CyaB2. Biswas KH, Badireddy S, Rajendran A, Anand GS, Visweswariah SS. PeerJ 3 e882 (2015)
  9. Intramolecular signaling in tandem-GAF domains from PDE5 and PDE10 studied with a cyanobacterial adenylyl cyclase reporter. Banjac A, Zimmermann MO, Boeckler FM, Kurz U, Schultz A, Schultz JE. Cell Signal 24 629-634 (2012)
  10. Structural Analysis of the Regulatory GAF Domains of cGMP Phosphodiesterase Elucidates the Allosteric Communication Pathway. Gupta R, Liu Y, Wang H, Nordyke CT, Puterbaugh RZ, Cui W, Varga K, Chu F, Ke H, Vashisth H, Cote RH. J Mol Biol 432 5765-5783 (2020)


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