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Crystal structure of CHP2 complexed with NHE1-cytosolic region and an implication for pH regulation.

Ammar YB, Takeda S, Hisamitsu T, Mori H, Wakabayashi S
EMBO J 25 2315-25 (2006)
Cited: 46 times
EuropePMC logo PMID: 16710297

Abstract

The plasma membrane Na+/H+ exchangers (NHE) require calcineurin B homologous protein (CHP) as an obligatory binding partner for ion transport. Here, we report the first crystal structure of CHP (CHP2 isoform) in complex with its binding domain in NHE1. We show that the cytoplasmic alpha-helix of NHE1 is inserted into the hydrophobic cleft formed by N- and C-lobes of CHP2 and that the size and shape of this crevice together with hydrogen bond formation at multiple positions assure a high degree of specificity for interaction with NHE members. Structure-based mutagenesis revealed the importance of hydrophobic interactions between CHP/NHE1 for the function of NHE1. Furthermore, the crystal structure shows the existence of a protruding CHP-unique region, and deletion of this region in CHP2 inhibited the NHE1 activity by inducing the acidic shift of intracellular pH dependence, while preserving interaction with NHE1. These findings suggest that CHP serves as an obligatory subunit that is required both for supporting the basic activity and regulating the pH-sensing of NHE1 via interactions between distinct parts of these proteins.

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  1. The structure of the C-terminal domain of the protein kinase AtSOS2 bound to the calcium sensor AtSOS3. Sánchez-Barrena MJ, Fujii H, Angulo I, Martínez-Ripoll M, Zhu JK, Albert A. Mol Cell 26 427-435 (2007)
  2. Crystal structure of CHP2 complexed with NHE1-cytosolic region and an implication for pH regulation. Ammar YB, Takeda S, Hisamitsu T, Mori H, Wakabayashi S. EMBO J 25 2315-2325 (2006)
  3. Highly precise protein-protein interaction prediction based on consensus between template-based and de novo docking methods. Ohue M, Matsuzaki Y, Shimoda T, Ishida T, Akiyama Y. BMC Proc 7 S6 (2013)
  4. Small-molecule binding sites to explore protein-protein interactions in the cancer proteome. Xu D, Jalal SI, Sledge GW, Meroueh SO. Mol Biosyst 12 3067-3087 (2016)
  5. 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)


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  1. SLC9/NHE gene family, a plasma membrane and organellar family of Na⁺/H⁺ exchangers. Donowitz M, Ming Tse C, Fuster D. Mol Aspects Med 34 236-251 (2013)
  2. Regulatory binding partners and complexes of NHE3. Donowitz M, Li X. Physiol Rev 87 825-872 (2007)
  3. NHE3 regulatory complexes. Donowitz M, Mohan S, Zhu CX, Chen TE, Lin R, Cha B, Zachos NC, Murtazina R, Sarker R, Li X. J Exp Biol 212 1638-1646 (2009)
  4. Beyond ion translocation: structural functions of the sodium-hydrogen exchanger isoform-1. Meima ME, Mackley JR, Barber DL. Curr Opin Nephrol Hypertens 16 365-372 (2007)
  5. Regulation of the Na(+)/H(+) exchanger in the healthy and diseased myocardium. Fliegel L. Expert Opin Ther Targets 13 55-68 (2009)
  6. Regulation of the cardiac Na⁺/H⁺ exchanger in health and disease. Wakabayashi S, Hisamitsu T, Nakamura TY. J Mol Cell Cardiol 61 68-76 (2013)
  7. Calcineurin homologous protein: a multifunctional Ca2+-binding protein family. Di Sole F, Vadnagara K, Moe OW, Babich V. Am J Physiol Renal Physiol 303 F165-79 (2012)
  8. The epithelial brush border Na+/H+ exchanger NHE3 associates with the actin cytoskeleton by binding to ezrin directly and via PDZ domain-containing Na+/H+ exchanger regulatory factor (NHERF) proteins. Cha B, Donowitz M. Clin Exp Pharmacol Physiol 35 863-871 (2008)
  9. Structural and functional insights into the cardiac Na⁺/H⁺ exchanger. Lee BL, Sykes BD, Fliegel L. J Mol Cell Cardiol 61 60-67 (2013)
  10. Inside out: targeting NHE1 as an intracellular and extracellular regulator of cancer progression. Provost JJ, Wallert MA. Chem Biol Drug Des 81 85-101 (2013)
  11. Emerging roles of the single EF-hand Ca2+ sensor tescalcin in the regulation of gene expression, cell growth and differentiation. Kolobynina KG, Solovyova VV, Levay K, Rizvanov AA, Slepak VZ. J Cell Sci 129 3533-3540 (2016)
  12. Trafficking Ion Transporters to the Apical Membrane of Polarized Intestinal Enterocytes. Engevik AC, Goldenring JR. Cold Spring Harb Perspect Biol 10 a027979 (2018)
  13. How Does Our Knowledge on the Na+/H+ Exchanger NHE1 Obtained by Biochemical and Molecular Analyses Keep up With Its Recent Structure Determination? Poet M, Doyen D, Van Obberghen E, Jarretou G, Bouret Y, Counillon L. Front Physiol 13 907587 (2022)
  14. Host Susceptibility to Nontuberculous Mycobacterial Pulmonary Disease. Namkoong H, Holland SM. Clin Chest Med 44 723-730 (2023)

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  2. The crystal structure of plant-specific calcium-binding protein AtCBL2 in complex with the regulatory domain of AtCIPK14. Akaboshi M, Hashimoto H, Ishida H, Saijo S, Koizumi N, Sato M, Shimizu T. J Mol Biol 377 246-257 (2008)
  3. Calcineurin B homologous protein 3 promotes the biosynthetic maturation, cell surface stability, and optimal transport of the Na+/H+ exchanger NHE1 isoform. Zaun HC, Shrier A, Orlowski J. J Biol Chem 283 12456-12467 (2008)
  4. Structure of human Na+/H+ exchanger NHE1 regulatory region in complex with calmodulin and Ca2+. Köster S, Pavkov-Keller T, Kühlbrandt W, Yildiz Ö. J Biol Chem 286 40954-40961 (2011)
  5. Na(+)/H(+) exchanger 1 directly binds to calcineurin A and activates downstream NFAT signaling, leading to cardiomyocyte hypertrophy. Hisamitsu T, Nakamura TY, Wakabayashi S. Mol Cell Biol 32 3265-3280 (2012)
  6. The calcineurin homologous protein-1 increases Na(+)/H(+) -exchanger 3 trafficking via ezrin phosphorylation. Di Sole F, Babich V, Moe OW. J Am Soc Nephrol 20 1776-1786 (2009)
  7. SLC9A9 mutations, gene expression, and protein-protein interactions in rat models of attention-deficit/hyperactivity disorder. Zhang-James Y, DasBanerjee T, Sagvolden T, Middleton FA, Faraone SV. Am J Med Genet B Neuropsychiatr Genet 156B 835-843 (2011)
  8. Novel phorbol ester-binding motif mediates hormonal activation of Na+/H+ exchanger. Wakabayashi S, Nakamura TY, Kobayashi S, Hisamitsu T. J Biol Chem 285 26652-26661 (2010)
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  10. The role of translation elongation factor eEF1A in intracellular alkalinization-induced tumor cell growth. Kim J, Namkung W, Yoon JS, Jo MJ, Lee SH, Kim KH, Kim JY, Lee MG. Lab Invest 89 867-874 (2009)
  11. Characterization of cytoskeletal protein 4.1R interaction with NHE1 (Na(+)/H(+) exchanger isoform 1). Nunomura W, Denker SP, Barber DL, Takakuwa Y, Gascard P. Biochem J 446 427-435 (2012)
  12. Functional importance of charged residues within the putative intracellular loops in pH regulation by Na+/ H+ exchanger NHE1. Hisamitsu T, Yamada K, Nakamura TY, Wakabayashi S. FEBS J 274 4326-4335 (2007)
  13. Regulation of intracellular pH by p90Rsk-dependent activation of an Na(+)/H(+) exchanger in starfish oocytes. Harada K, Fukuda E, Hirohashi N, Chiba K. J Biol Chem 285 24044-24054 (2010)
  14. A calcineurin homologous protein is required for sodium-proton exchange events in the C. elegans intestine. Wagner J, Allman E, Taylor A, Ulmschneider K, Kovanda T, Ulmschneider B, Nehrke K, Peters MA. Am J Physiol Cell Physiol 301 C1389-403 (2011)
  15. Evidence that Na+/H+ exchanger 1 is an ATP-binding protein. Shimada-Shimizu N, Hisamitsu T, Nakamura TY, Wakabayashi S. FEBS J 280 1430-1442 (2013)
  16. Nonsynonymous single nucleotide polymorphisms of NHE3 differentially decrease NHE3 transporter activity. Zhu XC, Sarker R, Horton JR, Chakraborty M, Chen TE, Tse CM, Cha B, Donowitz M. Am J Physiol Cell Physiol 308 C758-66 (2015)
  17. Nuclear accumulation of calcineurin B homologous protein 2 (CHP2) results in enhanced proliferation of tumor cells. Li QH, Wang LH, Lin YN, Chang GQ, Li HW, Jin WN, Hu RH, Pang TX. Genes Cells 16 416-426 (2011)
  18. Phosphorylation of NHE3-S719 regulates NHE3 activity through the formation of multiple signaling complexes. Sarker R, Cha B, Kovbasnjuk O, Cole R, Gabelli S, Tse CM, Donowitz M. Mol Biol Cell 28 1754-1767 (2017)
  19. The biophysical and molecular basis of intracellular pH sensing by Na+/H+ exchanger-3. Babich V, Vadnagara K, Di Sole F. FASEB J 27 4646-4658 (2013)
  20. The intracellular lipid-binding domain of human Na+/H+ exchanger 1 forms a lipid-protein co-structure essential for activity. Hendus-Altenburger R, Vogensen J, Pedersen ES, Luchini A, Araya-Secchi R, Bendsoe AH, Prasad NS, Prestel A, Cardenas M, Pedraz-Cuesta E, Arleth L, Pedersen SF, Kragelund BB. Commun Biol 3 731 (2020)
  21. Calcineurin homologous proteins regulate the membrane localization and activity of sodium/proton exchangers in C. elegans. Allman E, Wang Q, Walker RL, Austen M, Peters MA, Nehrke K. Am J Physiol Cell Physiol 310 C233-42 (2016)
  22. The C. elegans CHP1 homolog, pbo-1, functions in innate immunity by regulating the pH of the intestinal lumen. Benomar S, Lansdon P, Bender AM, Peterson BR, Chandler JR, Ackley BD. PLoS Pathog 16 e1008134 (2020)
  23. The effects of angiotensin-(1-7) on the exchanger NHE3 and on [Ca2+]i in the proximal tubules of spontaneously hypertensive rats. Castelo-Branco RC, Leite-Dellova DCA, Fernandes FB, Malnic G, de Mello-Aires M. Am J Physiol Renal Physiol 313 F450-F460 (2017)
  24. Exonic splicing code and protein binding sites for calcium. Pengelly RJ, Bakhtiar D, Borovská I, Královičová J, Vořechovský I. Nucleic Acids Res 50 5493-5512 (2022)
  25. Calcineurin B homologous protein 3 binds with high affinity to the CHP binding domain of the human sodium/proton exchanger NHE1. Fuchs S, Hansen SC, Markones M, Mymrikov EV, Heerklotz H, Hunte C. Sci Rep 8 14837 (2018)
  26. Conformational regulation and target-myristoyl switch of calcineurin B homologous protein 3. Becker F, Fuchs S, Refisch L, Drepper F, Bildl W, Schulte U, Liang S, Heinicke JI, Hansen SC, Kreutz C, Warscheid B, Fakler B, Mymrikov EV, Hunte C. Elife 12 e83868 (2023)
  27. Involvement of CHP2 in the Development of Non-Small Cell Lung Cancer and Patients' Poor Prognosis. Xu L, Qin Y, Sun B, Wang H, Gu J, Tang Z, Zhang W, Feng J. Appl Immunohistochem Mol Morphol 28 678-686 (2020)


Related citations provided by authors (1)

  1. Crystallization and preliminary crystallographic analysis of the human calcineurin homologous protein CHP2 bound to the cytoplasmic region of the Na+/H+ exchanger NHE1. Ben Ammar Y, Takeda S, Sugawara M, Miyano M, Mori H, Wakabayashi S Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 61 956-958 (2005)

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