1tbw › Citations

Ligand-induced conformational shift in the N-terminal domain of GRP94, an Hsp90 chaperone.

Immormino RM, Dollins DE, Shaffer PL, Soldano KL, Walker MA, Gewirth DT
J Biol Chem 279 46162-71 (2004)
Related entries: 1tc0, 1tc6

Cited: 68 times
EuropePMC logo PMID: 15292259

Abstract

GRP94 is the endoplasmic reticulum paralog of cytoplasmic Hsp90. Models of Hsp90 action posit an ATP-dependent conformational switch in the N-terminal ligand regulatory domain of the chaperone. However, crystal structures of the isolated N-domain of Hsp90 in complex with a variety of ligands have yet to demonstrate such a conformational change. We have determined the structure of the N-domain of GRP94 in complex with ATP, ADP, and AMP. Compared with the N-ethylcarboxamidoadenosine and radicicol-bound forms, these structures reveal a large conformational rearrangement in the protein. The nucleotide-bound form exposes new surfaces that interact to form a biochemically plausible dimer that is reminiscent of those seen in structures of MutL and DNA gyrase. Weak ATP binding and a conformational change in response to ligand identity are distinctive mechanistic features of GRP94 and suggest a model for how GRP94 functions in the absence of co-chaperones and ATP hydrolysis.

Reviews - 1tbw mentioned but not cited (1)

  1. Conformational dynamics of the molecular chaperone Hsp90. Krukenberg KA, Street TO, Lavery LA, Lavery LA, Agard DA. Q Rev Biophys 44 229-255 (2011)

Articles - 1tbw mentioned but not cited (1)

  1. Analysis of HSP90-related folds with MED-SuMo classification approach. Doppelt-Azeroual O, Moriaud F, Delfaud F, de Brevern AG. Drug Des Devel Ther 3 59-72 (2009)


Reviews citing this publication (18)

  1. Structure and mechanism of the Hsp90 molecular chaperone machinery. Pearl LH, Prodromou C. Annu Rev Biochem 75 271-294 (2006)
  2. In and out of the ER: protein folding, quality control, degradation, and related human diseases. Hebert DN, Molinari M. Physiol Rev 87 1377-1408 (2007)
  3. The HSP90 Family: Structure, Regulation, Function, and Implications in Health and Disease. Hoter A, El-Sabban ME, Naim HY. Int J Mol Sci 19 E2560 (2018)
  4. GRP94: An HSP90-like protein specialized for protein folding and quality control in the endoplasmic reticulum. Marzec M, Eletto D, Argon Y. Biochim Biophys Acta 1823 774-787 (2012)
  5. GRP94 in ER quality control and stress responses. Eletto D, Dersh D, Argon Y. Semin Cell Dev Biol 21 479-485 (2010)
  6. Structure, Function, and Regulation of the Hsp90 Machinery. Biebl MM, Buchner J. Cold Spring Harb Perspect Biol 11 a034017 (2019)
  7. Organellar calcium buffers. Prins D, Michalak M. Cold Spring Harb Perspect Biol 3 a004069 (2011)
  8. Role of HSP90 in Cancer. Birbo B, Madu EE, Madu CO, Jain A, Lu Y. Int J Mol Sci 22 10317 (2021)
  9. Single molecule studies of DNA mismatch repair. Erie DA, Weninger KR. DNA Repair (Amst) 20 71-81 (2014)
  10. The endoplasmic reticulum: A hub of protein quality control in health and disease. Vincenz-Donnelly L, Hipp MS. Free Radic Biol Med 108 383-393 (2017)
  11. Targeting Plasmodium falciparum Hsp90: Towards Reversing Antimalarial Resistance. Shahinas D, Folefoc A, Pillai DR. Pathogens 2 33-54 (2013)
  12. Secreted heat shock protein gp96-Ig: next-generation vaccines for cancer and infectious diseases. Strbo N, Garcia-Soto A, Schreiber TH, Podack ER. Immunol Res 57 311-325 (2013)
  13. Heat shock proteins HSP70 and GP96: structural insights. Facciponte JG, Wang XY, MacDonald IJ, Park JE, Arnouk H, Grimm MJ, Li Y, Kim H, Manjili MH, Easton DP, Subjeck JR. Cancer Immunol Immunother 55 339-346 (2006)
  14. Allogeneic tumor-cell-based vaccines secreting endoplasmic reticulum chaperone gp96. Podack ER, Raez LE. Expert Opin Biol Ther 7 1679-1688 (2007)
  15. Heat-shock protein 90 (Hsp90) as anticancer target for drug discovery: an ample computational perspective. Kumalo HM, Bhakat S, Bhakat S, Soliman ME. Chem Biol Drug Des 86 1131-1160 (2015)
  16. Inhibitors of the Plasmodium falciparum Hsp90 towards Selective Antimalarial Drug Design: The Past, Present and Future. Stofberg ML, Caillet C, de Villiers M, Zininga T. Cells 10 2849 (2021)
  17. The biology and inhibition of glucose-regulated protein 94/gp96. Pugh KW, Alnaed M, Brackett CM, Blagg BSJ. Med Res Rev 42 2007-2024 (2022)
  18. The Role of HSP90 Inhibitors in the Treatment of Cardiovascular Diseases. Qi S, Yi G, Yu K, Feng C, Deng S. Cells 11 3444 (2022)

Articles citing this publication (48)

  1. Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complex. Ali MM, Roe SM, Vaughan CK, Meyer P, Panaretou B, Piper PW, Prodromou C, Pearl LH. Nature 440 1013-1017 (2006)
  2. Structures of GRP94-nucleotide complexes reveal mechanistic differences between the hsp90 chaperones. Dollins DE, Warren JJ, Immormino RM, Gewirth DT. Mol Cell 28 41-56 (2007)
  3. Direct visualization of asymmetric adenine-nucleotide-induced conformational changes in MutL alpha. Sacho EJ, Kadyrov FA, Modrich P, Kunkel TA, Erie DA. Mol Cell 29 112-121 (2008)
  4. Spatially and kinetically resolved changes in the conformational dynamics of the Hsp90 chaperone machine. Graf C, Stankiewicz M, Kramer G, Mayer MP. EMBO J 28 602-613 (2009)
  5. Development of a Grp94 inhibitor. Duerfeldt AS, Peterson LB, Maynard JC, Ng CL, Eletto D, Ostrovsky O, Shinogle HE, Moore DS, Argon Y, Nicchitta CV, Blagg BS. J Am Chem Soc 134 9796-9804 (2012)
  6. Modeling signal propagation mechanisms and ligand-based conformational dynamics of the Hsp90 molecular chaperone full-length dimer. Morra G, Verkhivker G, Colombo G. PLoS Comput Biol 5 e1000323 (2009)
  7. The ATPase cycle of the mitochondrial Hsp90 analog Trap1. Leskovar A, Wegele H, Werbeck ND, Buchner J, Reinstein J. J Biol Chem 283 11677-11688 (2008)
  8. Nucleotide-dependent interaction of Saccharomyces cerevisiae Hsp90 with the cochaperone proteins Sti1, Cpr6, and Sba1. Johnson JL, Halas A, Flom G. Mol Cell Biol 27 768-776 (2007)
  9. Structures of the N-terminal and middle domains of E. coli Hsp90 and conformation changes upon ADP binding. Huai Q, Wang H, Liu Y, Kim HY, Toft D, Ke H. Structure 13 579-590 (2005)
  10. Structural basis for species-selective targeting of Hsp90 in a pathogenic fungus. Whitesell L, Robbins N, Huang DS, McLellan CA, Shekhar-Guturja T, LeBlanc EV, Nation CS, Hui R, Hutchinson A, Collins C, Chatterjee S, Trilles R, Xie JL, Krysan DJ, Lindquist S, Porco JA, Tatu U, Brown LE, Pizarro J, Cowen LE. Nat Commun 10 402 (2019)
  11. Targeted mutation of the mouse Grp94 gene disrupts development and perturbs endoplasmic reticulum stress signaling. Mao C, Wang M, Luo B, Wey S, Dong D, Wesselschmidt R, Rawlings S, Lee AS. PLoS One 5 e10852 (2010)
  12. Structure of unliganded GRP94, the endoplasmic reticulum Hsp90. Basis for nucleotide-induced conformational change. Dollins DE, Immormino RM, Gewirth DT. J Biol Chem 280 30438-30447 (2005)
  13. Experimental and structural testing module to analyze paralogue-specificity and affinity in the Hsp90 inhibitors series. Taldone T, Patel PD, Patel M, Patel HJ, Evans CE, Rodina A, Ochiana S, Shah SK, Uddin M, Gewirth D, Chiosis G. J Med Chem 56 6803-6818 (2013)
  14. An essential role for ATP binding and hydrolysis in the chaperone activity of GRP94 in cells. Ostrovsky O, Makarewich CA, Snapp EL, Argon Y. Proc Natl Acad Sci U S A 106 11600-11605 (2009)
  15. Different poses for ligand and chaperone in inhibitor-bound Hsp90 and GRP94: implications for paralog-specific drug design. Immormino RM, Metzger LE, Reardon PN, Dollins DE, Blagg BS, Gewirth DT. J Mol Biol 388 1033-1042 (2009)
  16. Understanding ligand-based modulation of the Hsp90 molecular chaperone dynamics at atomic resolution. Colombo G, Morra G, Meli M, Verkhivker G. Proc Natl Acad Sci U S A 105 7976-7981 (2008)
  17. Grp94, the endoplasmic reticulum Hsp90, has a similar solution conformation to cytosolic Hsp90 in the absence of nucleotide. Krukenberg KA, Böttcher UM, Southworth DR, Agard DA. Protein Sci 18 1815-1827 (2009)
  18. Development of Glucose Regulated Protein 94-Selective Inhibitors Based on the BnIm and Radamide Scaffold. Crowley VM, Khandelwal A, Mishra S, Stothert AR, Huard DJ, Zhao J, Muth A, Duerfeldt AS, Kizziah JL, Lieberman RL, Dickey CA, Blagg BS. J Med Chem 59 3471-3488 (2016)
  19. Plant endoplasmin supports the protein secretory pathway and has a role in proliferating tissues. Klein EM, Mascheroni L, Pompa A, Ragni L, Weimar T, Lilley KS, Dupree P, Vitale A. Plant J 48 657-673 (2006)
  20. Structure-activity relationship in a purine-scaffold compound series with selectivity for the endoplasmic reticulum Hsp90 paralog Grp94. Patel HJ, Patel PD, Ochiana SO, Yan P, Sun W, Patel MR, Shah SK, Tramentozzi E, Brooks J, Bolaender A, Shrestha L, Stephani R, Finotti P, Leifer C, Li Z, Gewirth DT, Taldone T, Chiosis G. J Med Chem 58 3922-3943 (2015)
  21. Structure of the ATP-binding domain of Plasmodium falciparum Hsp90. Corbett KD, Berger JM. Proteins 78 2738-2744 (2010)
  22. Structural and Functional Analysis of GRP94 in the Closed State Reveals an Essential Role for the Pre-N Domain and a Potential Client-Binding Site. Huck JD, Que NL, Hong F, Li Z, Gewirth DT. Cell Rep 20 2800-2809 (2017)
  23. Structure insights into mechanisms of ATP hydrolysis and the activation of human heat-shock protein 90. Li J, Sun L, Xu C, Yu F, Zhou H, Zhao Y, Zhang J, Cai J, Mao C, Tang L, Xu Y, He J. Acta Biochim Biophys Sin (Shanghai) 44 300-306 (2012)
  24. Congress Hsp90: from structure to phenotype. Jackson SE, Queitsch C, Toft D. Nat Struct Mol Biol 11 1152-1155 (2004)
  25. Identification of novel quaternary domain interactions in the Hsp90 chaperone, GRP94. Chu F, Maynard JC, Chiosis G, Nicchitta CV, Burlingame AL. Protein Sci 15 1260-1269 (2006)
  26. Mitochondrial Hsp90 is a ligand-activated molecular chaperone coupling ATP binding to dimer closure through a coiled-coil intermediate. Sung N, Lee J, Kim JH, Chang C, Joachimiak A, Lee S, Tsai FT. Proc Natl Acad Sci U S A 113 2952-2957 (2016)
  27. Probing molecular mechanisms of the Hsp90 chaperone: biophysical modeling identifies key regulators of functional dynamics. Dixit A, Verkhivker GM. PLoS One 7 e37605 (2012)
  28. Conformational lability of two molecular chaperones Hsc70 and gp96: effects of pH and temperature. Fan H, Kashi RS, Middaugh CR. Arch Biochem Biophys 447 34-45 (2006)
  29. A purine analog synergizes with chloroquine (CQ) by targeting Plasmodium falciparum Hsp90 (PfHsp90). Shahinas D, Folefoc A, Taldone T, Chiosis G, Crandall I, Pillai DR. PLoS One 8 e75446 (2013)
  30. Binding of the viral immunogenic octapeptide VSV8 to native glucose-regulated protein Grp94 (gp96) and its inhibition by the physiological ligands ATP and Ca2+. Ying M, Flatmark T. FEBS J 273 513-522 (2006)
  31. Effects of heat shock protein gp96 on human dendritic cell maturation and CTL expansion. Zhang Y, Zan Y, Shan M, Liu C, Shi M, Li W, Zhang Z, Liu N, Wang F, Zhong W, Liao F, Gao GF, Tien P. Biochem Biophys Res Commun 344 581-587 (2006)
  32. Structure Based Design of a Grp94-Selective Inhibitor: Exploiting a Key Residue in Grp94 To Optimize Paralog-Selective Binding. Que NLS, Crowley VM, Duerfeldt AS, Zhao J, Kent CN, Blagg BSJ, Gewirth DT. J Med Chem 61 2793-2805 (2018)
  33. Linking Nitrogen Load to the Structure and Function of Wetland Soil and Rhizosphere Microbial Communities. Hester ER, Harpenslager SF, van Diggelen JMH, Lamers LL, Jetten MSM, Lüke C, Lücker S, Welte CU. mSystems 3 e00214-17 (2018)
  34. Ribosome Profiling Reveals HSP90 Inhibitor Effects on Stage-Specific Protein Synthesis in Leishmania donovani. Bifeld E, Lorenzen S, Bartsch K, Vasquez JJ, Siegel TN, Clos J. mSystems 3 e00214-18 (2018)
  35. Genome Wide In silico Analysis of the Mismatch Repair Components of Plasmodium falciparum and Their Comparison with Human Host. Tarique M, Ahmad M, Chauhan M, Tuteja R. Front Microbiol 8 130 (2017)
  36. Experimental Anti-Inflammatory Drug Semapimod Inhibits TLR Signaling by Targeting the TLR Chaperone gp96. Wang J, Grishin AV, Ford HR. J Immunol 196 5130-5137 (2016)
  37. Napyradiomycins CNQ525.510B and A80915C target the Hsp90 paralogue Grp94. Farnaes L, La Clair JJ, Fenical W. Org Biomol Chem 12 418-423 (2014)
  38. General Structural and Functional Features of Molecular Chaperones. Edkins AL, Boshoff A. Adv Exp Med Biol 1340 11-73 (2021)
  39. cDNA cloning and expression of grp94 in the Pacific oyster Crassostrea gigas. Kawabe S, Yokoyama Y. Comp Biochem Physiol B Biochem Mol Biol 154 290-297 (2009)
  40. Exploring the Functional Complementation between Grp94 and Hsp90. Maharaj KA, Que NL, Hong F, Huck JD, Gill SK, Wu S, Li Z, Gewirth DT. PLoS One 11 e0166271 (2016)
  41. The endoplasmic reticulum chaperone BiP is a closure-accelerating cochaperone of Grp94. Huang B, Sun M, Hoxie R, Kotler JLM, Friedman LJ, Gelles J, Street TO. Proc Natl Acad Sci U S A 119 e2118793119 (2022)
  42. Role of Hsp90 in Plasmodium falciparum Malaria. Shahinas D, Pillai DR. Adv Exp Med Biol 1340 125-139 (2021)
  43. Basolateral expression of GRP94 in parietal cells of gastric mucosa. Arin RM, Rueda Y, Casis O, Gallego M, Vallejo AI, Ochoa B. Biochemistry (Mosc) 79 8-15 (2014)
  44. Secretion of a low-molecular-weight species of endogenous GRP94 devoid of the KDEL motif during endoplasmic reticulum stress in Chinese hamster ovary cells. Samy A, Yamano-Adachi N, Koga Y, Omasa T. Traffic 22 425-438 (2021)
  45. Molecular characterization of heat-shock protein 90 gene and its expression in Gobiocypris rarus juveniles exposed to pentachlorophenol. Liu Q, Huang S, Deng C, Xiong L, Gao X, Chen Y, Niu C, Liu Y. Fish Physiol Biochem 41 1279-1291 (2015)
  46. Genome-wide analysis of HSP90 gene family in the Mediterranean olive (Olea europaea subsp. europaea) provides insight into structural patterns, evolution and functional diversity. Bettaieb I, Hamdi J, Bouktila D. Physiol Mol Biol Plants 26 2301-2318 (2020)
  47. Insight into the Nucleotide Based Modulation of the Grp94 Molecular Chaperone Using Multiscale Dynamics. Alao JP, Obaseki I, Amankwah YS, Nguyen Q, Sugoor M, Unruh E, Popoola HO, Tehver R, Kravats AN. J Phys Chem B 127 5389-5409 (2023)
  48. Visualization of conformational transition of GRP94 in solution. Sun S, Zhu R, Zhu M, Wang Q, Li N, Yang B. Life Sci Alliance 7 e202302051 (2024)


Quick links