Hormone affinity and fibril formation of piscine transthyretin: The role of the N-terminal

Morgado, Isabel; Melo, Eduardo P.; Lundberg, Erik; Estrela, Nídia; Sauer‐Eriksson, A. Elisabeth; Power, Deborah M.

doi:10.1016/j.mce.2008.06.010

Cited by 15 publications

(8 citation statements)

References 69 publications

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“…Furthermore, depending on the conditions used, fibrils of different morphology were obtained. Recent studies have shown that sbTTR binds thioflavin-T (ThT) at low pH, suggestive of amyloid [33]. In our study, we verified that sbTTR forms fibrillar structures at low pH that are similar in shape to those of hTTR.…”

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confidence: 84%

Stability and fibril formation properties of human and fish transthyretin, and of theEscherichia colitransthyretin‐related protein

et al. 2009

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Human transthyretin (hTTR) is one of several proteins known to cause amyloid disease. Conformational changes in its native structure result in aggregation of the protein, leading to insoluble amyloid fibrils. The transthyretin (TTR)‐related proteins comprise a protein family of 5‐hydroxyisourate hydrolases with structural similarity to TTR. In this study, we tested the amyloidogenic properties, if any, of sea bream TTR (sbTTR) and Escherichia coli transthyretin‐related protein (ecTRP), which share 52% and 30% sequence identity, respectively, with hTTR. We obtained filamentous structures from all three proteins under various conditions, but, interestingly, different structures displayed different tinctorial properties. hTTR and sbTTR formed thin, curved fibrils at low pH (pH 2–3) that bound thioflavin‐T (thioflavin‐T‐positive) but did not stain with Congo Red (CR) (CR‐negative). Aggregates formed at the slightly higher pH of 4.0–5.5 had different morphology, displaying predominantly amorphous structures. CR‐positive material of hTTR was found in this material, in agreement with previous results. ecTRP remained soluble at pH 2–12 at ambient temperatures. By raising of the temperature, fibril formation could be induced at neutral pH in all three proteins. Most of these temperature‐induced fibrils were thicker and straighter than the in vitro fibrils seen at low pH. In other words, the temperature‐induced fibrils were more similar to fibrils seen in vivo. The melting temperature of ecTRP was 66.7 °C. This is approximately 30 °C lower than the melting temperatures of sbTTR and hTTR. Information from the crystal structures was used to identify possible explanations for the reduced thermostability of ecTRP.

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confidence: 84%

Stability and fibril formation properties of human and fish transthyretin, and of theEscherichia colitransthyretin‐related protein

et al. 2009

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“…In a previous study, comprising an analysis of chimeric TTRs that have had the N‐terminal sequence changed to that of a TTR of a different species, but which exist in nature, we demonstrated the involvement of the N‐terminal segment with respect to TTR in its binding with TH [29]. This involvement was subsequently confirmed using truncated TTRs [57]. However, only by shortening the amino acid sequence to an appropriate length could effect on the binding clearly be shown.…”

Section: Discussionmentioning

confidence: 55%

Effect of the N‐terminal sequence on the binding affinity of transthyretin for human retinol‐binding protein

Leelawatwattana

Praphanphoj²,

Prapunpoj

2011

The FEBS Journal

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During vertebrate evolution, the N-terminal region of transthyretin (TTR) subunit has undergone a change in both length and hydropathy. This was previously shown to change the binding affinity for thyroid hormones (THs). However, it was not known whether this change affects other functions of TTR. In the present study, the effect of these changes on the binding of TTR to retinol-binding protein (RBP) was determined. Two wild-type TTRs from human and Crocodylus porosus, and three chimeric TTRs, including a human chimeric TTR in which its N-terminal sequence was changed to that of C. porosus TTR (croc ⁄ huTTR) and two C. porosus chimeric TTRs (hu ⁄ crocTTR in which its N-terminal sequence was changed to that of human TTR and xeno ⁄ crocTTR in which its N-terminal sequence was changed to that of Xenopus laevis TTR), were analyzed for their binding to human RBP by native-PAGE followed by immunoblotting and a chemilluminescence assay. The K d of human TTR was 30.41 ± 2.03 lM, and was similar to that reported for the second binding site, whereas that of crocodile TTR was 2.19 ± 0.24 lM. The binding affinities increased in croc ⁄ huTTR (K d = 23.57 ± 3.54 lM) and xeno ⁄ crocTTR (K d = 0.61 ± 0.16 lM) in which their N-termini were longer and more hydrophobic, but decreased in hu ⁄ crocTTR (K d = 5.03 ± 0.68 lM) in which its N-terminal region was shorter and less hydrophobic. These results suggest an influence of the N-terminal primary structure of TTR on its function as a co-carrier for retinol with RBP.

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“…These data led to the postulation that the N‐terminal region has a role in determining the binding affinities of T3 and T4 for transthyretin. This hypothesis was subsequently supported by others using fish‐truncated transthyretin [55].…”

Section: Functions Of Transthyretinmentioning

confidence: 61%

“…During the evolution of vertebrates, the binding affinities of transthyretin to THs varied [8,16,37,39,55]. The binding to T4 increased, while the binding to T3 decreased, during the evolution of eutherians from their ancestors.…”

Section: Influence Of the N-terminal Structure On The Th Distributor mentioning

confidence: 99%

Evolutionary changes to transthyretin: structure–function relationships

Prapunpoj

Leelawatwattana

2009

The FEBS Journal

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Transthyretin is one of the three major thyroid hormone‐binding proteins in plasma and/or cerebrospinal fluid of vertebrates. It transports retinol via binding to retinol‐binding protein, and exists mainly as a homotetrameric protein of ∼ 55 kDa in plasma. The first 3D structure of transthyretin was an X‐ray crystal structure from human transthyretin. Elucidation of the structure–function relationship of transthyretin has been of significant interest since its highly conserved structure was shown to be associated with several aspects of metabolism and with human diseases such as amyloidosis. Transthyretin null mice do not have an overt phenotype, probably because transthyretin is part of a network with other thyroid hormone distributor proteins. Systematic study of the evolutionary changes of transthyretin structure is an effective way to elucidate its function. This review summarizes current knowledge about the evolution of structural and functional characteristics of vertebrate transthyretins. The molecular mechanism of evolutionary change and the resultant effects on the function of transthyretin are discussed.

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Hormone affinity and fibril formation of piscine transthyretin: The role of the N-terminal

Cited by 15 publications

References 69 publications

Stability and fibril formation properties of human and fish transthyretin, and of theEscherichia colitransthyretin‐related protein

Stability and fibril formation properties of human and fish transthyretin, and of theEscherichia colitransthyretin‐related protein

Effect of the N‐terminal sequence on the binding affinity of transthyretin for human retinol‐binding protein

Evolutionary changes to transthyretin: structure–function relationships

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