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Structural evidence for native state stabilization of a conformationally labile amyloidogenic transthyretin variant by fibrillogenesis inhibitors.

Zanotti G, Cendron L, Folli C, Florio P, Imbimbo BP, Berni R
FEBS Lett 587 2325-31 (2013)
Related entries: 2g3x, 2g3z, 2g4e, 2g4g, 2noy, 3djr, 3djs, 3djt, 3djz, 3dk0, 3dk2, 4i85, 4i89

Cited: 12 times
EuropePMC logo PMID: 23792159

Abstract

Several classes of chemicals are able to bind to the thyroxine binding sites of transthyretin (TTR), stabilizing its native state and inhibiting in vitro the amyloidogenic process. The amyloidogenic I84S TTR variant undergoes a large conformational change at moderately acidic pH. Structural evidence has been obtained by X-ray analysis for the native state stabilization of I84S TTR by two chemically distinct fibrillogenesis inhibitors. In fact, they fully prevent the acidic pH-induced protein conformational change as a result of a long-range stabilizing effect. This study provides further support to the therapeutic strategy based on the use of TTR stabilizers as anti-amyloidogenic drugs.

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  1. Predicting binding sites from unbound versus bound protein structures. Clark JJ, Orban ZJ, Carlson HA. Sci Rep 10 15856 (2020)


Articles citing this publication (11)

  1. Transthyretin Binding Heterogeneity and Anti-amyloidogenic Activity of Natural Polyphenols and Their Metabolites. Florio P, Folli C, Cianci M, Del Rio D, Zanotti G, Berni R. J Biol Chem 290 29769-29780 (2015)
  2. Transthyretin complexes with curcumin and bromo-estradiol: evaluation of solubilizing multicomponent mixtures. Ciccone L, Tepshi L, Nencetti S, Stura EA. N Biotechnol 32 54-64 (2015)
  3. A new crystal form of human transthyretin obtained with a curcumin derived ligand. Polsinelli I, Nencetti S, Shepard W, Ciccone L, Orlandini E, Stura EA. J Struct Biol 194 8-17 (2016)
  4. Structural evidence for asymmetric ligand binding to transthyretin. Cianci M, Folli C, Zonta F, Florio P, Berni R, Zanotti G. Acta Crystallogr D Biol Crystallogr 71 1582-1592 (2015)
  5. CHF5074 (CSP-1103) stabilizes human transthyretin in mice humanized at the transthyretin and retinol-binding protein loci. Mu Y, Jin S, Shen J, Sugano A, Takaoka Y, Qiang L, Imbimbo BP, Yamamura K, Li Z. FEBS Lett 589 849-856 (2015)
  6. Discovery of γ-Mangostin as an Amyloidogenesis Inhibitor. Yokoyama T, Ueda M, Ando Y, Mizuguchi M. Sci Rep 5 13570 (2015)
  7. Evaluating the effect of mutations and ligand binding on transthyretin homotetramer dynamics. Saldaño TE, Zanotti G, Parisi G, Fernandez-Alberti S. PLoS One 12 e0181019 (2017)
  8. Structural and dynamics evidence for scaffold asymmetric flexibility of the human transthyretin tetramer. Zanotti G, Vallese F, Ferrari A, Menozzi I, Saldaño TE, Berto P, Fernandez-Alberti S, Berni R. PLoS One 12 e0187716 (2017)
  9. Amyloid deposition in a mouse model humanized at the transthyretin and retinol-binding protein 4 loci. Li X, Lyu Y, Shen J, Mu Y, Qiang L, Liu L, Araki K, Imbimbo BP, Yamamura KI, Jin S, Li Z. Lab Invest 98 512-524 (2018)
  10. CSP-1103 (CHF5074) stabilizes human transthyretin in healthy human subjects. Qiang L, Guan Y, Li X, Liu L, Mu Y, Sugano A, Takaoka Y, Sakaeda T, Imbimbo BP, Yamamura KI, Jin S, Li Z. Amyloid 24 42-51 (2017)
  11. Turmeric effect on subcutaneous insulin-induced amyloid mass: an in vivo study. Kheirbakhsh R, Chinisaz M, Amanpour S, Amini S, Khodayari S, Khodayari H, Dilmaghanian A, Haddadi M, Ebrahim-Habibi A. Drug Chem Toxicol 40 1-6 (2017)


Related citations provided by authors (2)

  1. Acidic pH-induced conformational changes in amyloidogenic mutant transthyretin.. Pasquato N, Berni R, Folli C, Alfieri B, Cendron L, Zanotti G J Mol Biol 366 711-9 (2007)
  2. Amyloidogenic potential of transthyretin variants: insights from structural and computational analyses.. Cendron L, Trovato A, Seno F, Folli C, Alfieri B, Zanotti G, Berni R J Biol Chem 284 25832-41 (2009)

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