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Transthyretin stability as a key factor in amyloidogenesis: X-ray analysis at atomic resolution.

Sebastião MP, Lamzin V, Saraiva MJ, Damas AM
J Mol Biol 306 733-44 (2001)
Related entries: 1fh2, 1fhn

Cited: 49 times
EuropePMC logo PMID: 11243784

Abstract

Transthyretin (TTR) amyloidosis is a conformational disturbance, which, like other amyloidoses, represents a life threat. Here, we report a TTR variant, TTR Thr119Met, that has been shown to have a protective role in the development of clinical symptoms in carriers of TTR Val30Met, one of the most frequent variants among TTR amyloidosis patients. In order to understand this effect, we have determined the structures of the TTR Val30Met/Thr119Met double mutant isolated from the serum of one patient and of both the native and thyroxine complex of TTR Thr119Met. Major conclusions are: (i) new H-bonds within each monomer and monomer-monomer inter-subunit contacts, e.g. Ser117-Ser117 and Met119-Tyr114, increase protein stability, possibly leading to the protective effect of the TTR Val30Met/Thr119Met variant when compared to the single variant TTR Val30Met. (ii) The mutated residue (Met119) extends across the thyroxine binding channel inducing conformational changes that lead to closer contacts between different dimers within the tetramer. The data, at atomic resolution, were essential to detect, for the first time, the subtle changes in the inter-subunit contacts of TTR, and explain the non-amyloidogenic potential of the TTR Thr119Met variant, improving considerably current research on the TTR amyloid fibril formation pathway.

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  1. Halogen bonds in biological molecules. Auffinger P, Hays FA, Westhof E, Ho PS. Proc Natl Acad Sci U S A 101 16789-16794 (2004)
  2. Uncovering the Mechanism of Aggregation of Human Transthyretin. Saelices L, Johnson LM, Liang WY, Sawaya MR, Cascio D, Ruchala P, Whitelegge J, Jiang L, Riek R, Eisenberg DS. J Biol Chem 290 28932-28943 (2015)
  3. Human transthyretin in complex with iododiflunisal: structural features associated with a potent amyloid inhibitor. Gales L, Macedo-Ribeiro S, Arsequell G, Valencia G, Saraiva MJ, Damas AM. Biochem J 388 615-621 (2005)
  4. Stretching to understand proteins - a survey of the protein data bank. Sułkowska JI, Cieplak M. Biophys J 94 6-13 (2008)
  5. Generating properly weighted ensemble of conformations of proteins from sparse or indirect distance constraints. Lin M, Lu HM, Chen R, Liang J. J Chem Phys 129 094101 (2008)
  6. Specificity in molecular design: a physical framework for probing the determinants of binding specificity and promiscuity in a biological environment. Radhakrishnan ML, Tidor B. J Phys Chem B 111 13419-13435 (2007)
  7. Using neural networks and evolutionary information in decoy discrimination for protein tertiary structure prediction. Tan CW, Jones DT. BMC Bioinformatics 9 94 (2008)
  8. Rigorous treatment of multispecies multimode ligand-receptor interactions in 3D-QSAR: CoMFA analysis of thyroxine analogs binding to transthyretin. Natesan S, Wang T, Lukacova V, Bartus V, Khandelwal A, Balaz S. J Chem Inf Model 51 1132-1150 (2011)
  9. 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)
  10. Neutrophil Immunomodulatory Activity of Nerolidol, a Major Component of Essential Oils from Populus balsamifera Buds and Propolis. Schepetkin IA, Özek G, Özek T, Kirpotina LN, Kokorina PI, Khlebnikov AI, Quinn MT. Plants (Basel) 11 3399 (2022)


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  1. One mutation, two distinct disease variants: unravelling the impact of transthyretin amyloid fibril composition. Suhr OB, Lundgren E, Westermark P. J Intern Med 281 337-347 (2017)
  2. Transthyretin amyloidosis: a tale of weak interactions. Saraiva MJ. FEBS Lett 498 201-203 (2001)
  3. The workings of the amyloid diseases. Bellotti V, Nuvolone M, Giorgetti S, Obici L, Palladini G, Russo P, Lavatelli F, Perfetti V, Merlini G. Ann Med 39 200-207 (2007)
  4. Review on the Structures and Activities of Transthyretin Amyloidogenesis Inhibitors. Guo X, Liu Z, Zheng Y, Li Y, Li L, Liu H, Chen Z, Wu L. Drug Des Devel Ther 14 1057-1081 (2020)
  5. Structural aspects of thyroid hormone binding to proteins and competitive interactions with natural and synthetic compounds. Schweizer U, Towell H, Vit A, Rodriguez-Ruiz A, Steegborn C. Mol Cell Endocrinol 458 57-67 (2017)

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  1. Sequence-dependent denaturation energetics: A major determinant in amyloid disease diversity. Hammarström P, Jiang X, Hurshman AR, Powers ET, Kelly JW. Proc Natl Acad Sci U S A 99 Suppl 4 16427-16432 (2002)
  2. Transthyretin binding to A-Beta peptide--impact on A-Beta fibrillogenesis and toxicity. Costa R, Gonçalves A, Saraiva MJ, Cardoso I. FEBS Lett 582 936-942 (2008)
  3. Whole-genome sequence-based analysis of thyroid function. Taylor PN, Porcu E, Chew S, Campbell PJ, Traglia M, Brown SJ, Mullin BH, Shihab HA, Min J, Walter K, Memari Y, Huang J, Barnes MR, Beilby JP, Charoen P, Danecek P, Dudbridge F, Forgetta V, Greenwood C, Grundberg E, Johnson AD, Hui J, Lim EM, McCarthy S, Muddyman D, Panicker V, Perry JR, Bell JT, Yuan W, Relton C, Gaunt T, Schlessinger D, Abecasis G, Cucca F, Surdulescu GL, Woltersdorf W, Zeggini E, Zheng HF, Toniolo D, Dayan CM, Naitza S, Walsh JP, Spector T, Davey Smith G, Durbin R, Richards JB, Sanna S, Soranzo N, Timpson NJ, Wilson SG, UK0K Consortium. Nat Commun 6 5681 (2015)
  4. Kinetic stabilization of the native state by protein engineering: implications for inhibition of transthyretin amyloidogenesis. Foss TR, Kelker MS, Wiseman RL, Wilson IA, Kelly JW. J Mol Biol 347 841-854 (2005)
  5. Selective binding to transthyretin and tetramer stabilization in serum from patients with familial amyloidotic polyneuropathy by an iodinated diflunisal derivative. Almeida MR, Macedo B, Cardoso I, Alves I, Valencia G, Arsequell G, Planas A, Saraiva MJ. Biochem J 381 351-356 (2004)
  6. A molecular mechanism for transthyretin amyloidogenesis. Yee AW, Aldeghi M, Blakeley MP, Ostermann A, Mas PJ, Moulin M, de Sanctis D, Bowler MW, Mueller-Dieckmann C, Mitchell EP, Haertlein M, de Groot BL, Boeri Erba E, Forsyth VT. Nat Commun 10 925 (2019)
  7. Hydration and packing are crucial to amyloidogenesis as revealed by pressure studies on transthyretin variants that either protect or worsen amyloid disease. Ferrão-Gonzales AD, Palmieri L, Valory M, Silva JL, Lashuel H, Kelly JW, Foguel D. J Mol Biol 328 963-974 (2003)
  8. Binding and stabilization of transthyretin by curcumin. Pullakhandam R, Srinivas PN, Nair MK, Reddy GB. Arch Biochem Biophys 485 115-119 (2009)
  9. Assemblies of Alzheimer's peptides A beta 25-35 and A beta 31-35: reverse-turn conformation and side-chain interactions revealed by X-ray diffraction. Bond JP, Deverin SP, Inouye H, el-Agnaf OM, Teeter MM, Kirschner DA. J Struct Biol 141 156-170 (2003)
  10. Assessing the relative importance of the biophysical properties of amino acid substitutions associated with human genetic disease. Terp BN, Cooper DN, Christensen IT, Jørgensen FS, Bross P, Gregersen N, Krawczak M. Hum Mutat 20 98-109 (2002)
  11. Native state hydrogen exchange study of suppressor and pathogenic variants of transthyretin. Liu K, Kelly JW, Wemmer DE. J Mol Biol 320 821-832 (2002)
  12. 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 25832-25841 (2009)
  13. Iodine atoms: a new molecular feature for the design of potent transthyretin fibrillogenesis inhibitors. Mairal T, Nieto J, Pinto M, Almeida MR, Gales L, Ballesteros A, Barluenga J, Pérez JJ, Vázquez JT, Centeno NB, Saraiva MJ, Damas AM, Planas A, Arsequell G, Valencia G. PLoS One 4 e4124 (2009)
  14. Enthalpy-Driven Stabilization of Transthyretin by AG10 Mimics a Naturally Occurring Genetic Variant That Protects from Transthyretin Amyloidosis. Miller M, Pal A, Albusairi W, Joo H, Pappas B, Haque Tuhin MT, Liang D, Jampala R, Liu F, Khan J, Faaij M, Park M, Chan W, Graef I, Zamboni R, Kumar N, Fox J, Sinha U, Alhamadsheh M. J Med Chem 61 7862-7876 (2018)
  15. Human embryonic, fetal, and adult hemoglobins have different subunit interface strengths. Correlation with lifespan in the red cell. Manning LR, Russell JE, Padovan JC, Chait BT, Popowicz A, Manning RS, Manning JM. Protein Sci 16 1641-1658 (2007)
  16. Conformational flexibility tunes the propensity of transthyretin to form fibrils through non-native intermediate states. Das JK, Mall SS, Bej A, Mukherjee S. Angew Chem Int Ed Engl 53 12781-12784 (2014)
  17. Human TTR conformation altered by rhenium tris-carbonyl derivatives. Ciccone L, Policar C, Stura EA, Shepard W. J Struct Biol 195 353-364 (2016)
  18. Cooperative stabilization of transthyretin by clusterin and diflunisal. Greene MJ, Klimtchuk ES, Seldin DC, Berk JL, Connors LH. Biochemistry 54 268-278 (2015)
  19. Analysis of the TTR gene in the investigation of amyloidosis: A 25-year single UK center experience. Rowczenio D, Quarta CC, Fontana M, Whelan CJ, Martinez-Naharro A, Trojer H, Baginska A, Ferguson SM, Gilbertson J, Rezk T, Sachchithanantham S, Mahmood S, Manwani R, Sharpley F, Wechalekar AD, Hawkins PN, Gillmore JD, Lachmann HJ. Hum Mutat 40 90-96 (2019)
  20. Destabilization of transthyretin by pathogenic mutations in the DE loop. Takeuchi M, Mizuguchi M, Kouno T, Shinohara Y, Aizawa T, Demura M, Mori Y, Shinoda H, Kawano K. Proteins 66 716-725 (2007)
  21. Structure of Monomeric Transthyretin Carrying the Clinically Important T119M Mutation. Kim JH, Oroz J, Zweckstetter M. Angew Chem Int Ed Engl 55 16168-16171 (2016)
  22. The putative role of some conserved water molecules in the structure and function of human transthyretin. Banerjee A, Dasgupta S, Mukhopadhyay BP, Sekar K. Acta Crystallogr D Biol Crystallogr 71 2248-2266 (2015)
  23. Cavity filling mutations at the thyroxine-binding site dramatically increase transthyretin stability and prevent its aggregation. Sant'Anna R, Almeida MR, Varejāo N, Gallego P, Esperante S, Ferreira P, Pereira-Henriques A, Palhano FL, de Carvalho M, Foguel D, Reverter D, Saraiva MJ, Ventura S. Sci Rep 7 44709 (2017)
  24. A severe form of amyloidotic polyneuropathy in a Costa Rican family with a rare transthyretin mutation (Glu54Lys). Busse A, Sánchez MA, Monterroso V, Alvarado MV, León P. Am J Med Genet A 128A 190-194 (2004)
  25. Formation of cytotoxic transthyretin is not dependent on inter-molecular disulphide bridges commonly found within the amyloid form. Lindhagen-Persson M, Vestling M, Reixach N, Olofsson A. Amyloid 15 240-245 (2008)
  26. Structure-based analysis of A19D, a variant of transthyretin involved in familial amyloid cardiomyopathy. Ferreira P, Sant'Anna R, Varejão N, Lima C, Novis S, Barbosa RV, Caldeira CM, Rumjanek FD, Ventura S, Cruz MW, Foguel D. PLoS One 8 e82484 (2013)
  27. Conserved water mediated H-bonding dynamics of Ser117 and Thr119 residues in human transthyretin-thyroxin complexation: inhibitor modeling study through docking and molecular dynamics simulation. Banerjee A, Bairagya HR, Mukhopadhyay BP, Nandi TK, Mishra DK. J Mol Graph Model 44 70-80 (2013)
  28. Gene therapy approach to FAP: in vivo influence of T119M in TTR deposition in a transgenic V30M mouse model. Batista AR, Gianni D, Ventosa M, Coelho AV, Almeida MR, Sena-Esteves M, Saraiva MJ. Gene Ther 21 1041-1050 (2014)
  29. An insight to the conserved water mediated dynamics of catalytic His88 and its recognition to thyroxin and RBP binding residues in human transthyretin. Banerjee A, Mukhopadhyay BP. J Biomol Struct Dyn 33 1973-1988 (2015)
  30. Progress in transthyretin fibrillogenesis research strengthens the amyloid hypothesis. Chakrabartty A. Proc Natl Acad Sci U S A 98 14757-14759 (2001)
  31. Proposing a minimal set of metrics and methods to predict probabilities of amyloidosis disease and onset age in individuals. Criddle RS, Lin HL, James I, Park JS, Hansen LD, Price JC. Aging (Albany NY) 12 22356-22369 (2020)
  32. Development of a Highly Potent Transthyretin Amyloidogenesis Inhibitor: Design, Synthesis, and Evaluation. Pinheiro F, Pallarès I, Peccati F, Sánchez-Morales A, Varejão N, Bezerra F, Ortega-Alarcon D, Gonzalez D, Osorio M, Navarro S, Velázquez-Campoy A, Almeida MR, Reverter D, Busqué F, Alibés R, Sodupe M, Ventura S. J Med Chem 65 14673-14691 (2022)
  33. Nanoscale structural characterization of transthyretin aggregates formed at different time points of protein aggregation using atomic force microscopy-infrared spectroscopy. Rodriguez A, Ali A, Holman AP, Dou T, Zhaliazka K, Kurouski D. Protein Sci 32 e4838 (2023)
  34. 3-O-Methyltolcapone and Its Lipophilic Analogues Are Potent Inhibitors of Transthyretin Amyloidogenesis with High Permeability and Low Toxicity. Poonsiri T, Dell'Accantera D, Loconte V, Casnati A, Cervoni L, Arcovito A, Benini S, Ferrari A, Cipolloni M, Cacioni E, De Franco F, Giacchè N, Rinaldo S, Folli C, Sansone F, Berni R, Cianci M. Int J Mol Sci 25 479 (2023)


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