Crocodile transthyretin: structure, function, and evolution

Prapunpoj, Porntip; Richardson, Samantha; Schreiber, Gerhard

doi:10.1152/ajpregu.00042.2002

Cited by 31 publications

(66 citation statements)

References 53 publications

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“…This segment is shorter and more hydrophilic in eutherians becoming longer and more hydrophobic in marsupials (with two additional amino acids), and in birds, reptile and amphibian (with three additional amino acids). These changes could be explained by splice site shifts of intron 1 as previously proposed ( So far, binding studies involving recombinant chimeric xenopus/crocodile TTR and recently with human/crocodile TTR provided experimental evidence that this region influences TH binding affinity of TTR (Prapunpoj et al, 2006, Prapunpoj et al, 2002.…”

Section: Role Of the N-terminal Region On Sbttr Bindingmentioning

confidence: 63%

“…However, binding studies of plasma TTR with radiolabelled T 4 and T 3 have established that mammalian TTR has the highest affinity peer-00532040, version 1 -4 Nov 2010 M a n u s c r i p t 5 for T 4 while avian TTR preferentially binds T 3 (Chang et al, 1999). Similar preferences for T 3 were found for this protein in crocodile (Prapunpoj et al, 2002) and amphibians (Prapunpoj et al, 2000, Yamauchi et al, 1993. The molecular basis for the different affinity of mammalian and lower vertebrate TTR for the thyroid hormones remains to be established but it has been proposed that changes in the N-terminus of the protein may be an important factor.…”

Section: Introductionmentioning

confidence: 83%

“…This evolution is consistent with physiologically advantageous adaptations regarding TH transport in which T 4 acts as a precursor hormone liberated from the thyroid gland and conversion to T 3 occurs in a tissue-specific manner and is regulated by deiodinases. Prapunpoj et al, 2002), amphibians and fish (Eneqvist et al, 2003, Santos and Power, 1999, Yamauchi et al, 1993, Yamauchi et al, 1999. However, values reported so far to describe affinities between TTRs and THs are very variable between studies even for the same proteins, probably as a consequence of assay methods and protein origin (serum or recombinant).…”

Section: Evolution Of Transthyretin Binding Affinity For Ths T 3 and Tmentioning

confidence: 99%

“…TTR has now been identified in most vertebrate groups; it is present in placental mammals, Australian and American marsupials, birds, reptiles, amphibians and fish (Dickson et al, 1985, Duan et al, 1991, Duan et al, 1995, Larsson et al, 1985, Mita et al, 1984, Prapunpoj et al, 2002, Prapunpoj et al, 2000, Richardson et al, 1994, Santos and Power, 1996, Santos and Power, 1999, Yamauchi et al, 1993, Yamauchi et al, 1999. Moreover, recently a family of transthyretin-like peer-00532040, version 1 -4 Nov 2010…”

Section: Introductionmentioning

confidence: 99%

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

Morgado

Melo

Lundberg

et al. 2008

Molecular and Cellular Endocrinology

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SummaryTransthyretin (TTR) transports thyroid hormones (THs), thyroxine (T 4 ) and triiodothyronine (T 3 ) in the blood of vertebrates. TH-binding sites are highly conserved in vertebrate TTR however, piscine TTR has a longer N-terminus which is thought to influence TH-binding affinity and may influence TTR stability. We produced recombinant wild-type sea bream TTR (sbTTRWT) plus two mutants in which six (sbTTRM6) and twelve (sbTTRM12) N-terminal residues were removed. Ligandbinding studies revealed similar affinities for T 3 (Kd=10.6±1.7nM) and T 4 (Kd=9.8±0.97nM) binding to sbTTRWT. Affinity for THs was unaltered in sbTTRM12 but sbTTRM6 had poorer affinity for T 4 (Kd=252.3±15.8nM) implying that some residues in the N-terminus can influence T 4 binding. sbTTRM6 inhibited acid-mediated fibril formation in vitro as shown by fluorometric measurements using thioflavine-T. In contrast, fibril formation by sbTTRM12 was significant, probably due to decreased stability of the tetramer. Such studies also suggested that sbTTRWT is more resistant to fibril formation than human TTR.

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Section: Role Of the N-terminal Region On Sbttr Bindingmentioning

confidence: 63%

Section: Introductionmentioning

confidence: 83%

Section: Evolution Of Transthyretin Binding Affinity For Ths T 3 and Tmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Morgado

Melo

Lundberg

et al. 2008

Molecular and Cellular Endocrinology

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“…For example, in the most well known function of TTR as a distributor for THs, mammalian TTRs have the binding preference opposite to the other vertebrate TTRs. While mammalian TTRs bind T4 better than T3, the other vertebrate TTRs bind T3 better than T4 [15][16][17] . The preference of the binding with T4 in mammalian TTRs correlates with the increase of the relative size of cerebral cortex, the requirement for T4 movement from blood to the brain, and the homoeostasis of THs in the choroid plexus in particular for proper growth and differentiation of the central nervous system of the animals 18 .…”

Section: Introductionmentioning

confidence: 99%

Proteolytic activity of Crocodylus porosus transthyretin protease and role of the terminal polypeptide sequences

Leelawatwattana¹,

Praphanphoj²,

Prapunpoj³

2016

ScienceAsia

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Human transthyretin (TTR), a recently identified protease, participates in the biology of high density lipoprotein and in the nervous system. In the present study, we determined whether TTR from a non-mammal Crocodylus porosus (crocTTR) has proteolytic activity and whether the N-and C-termini of the TTR polypeptide affect the proteolytic activity. The proteolytic activity of crocTTR and three chimeric crocTTRs: xenoN/crocTTR (crocTTR in which the N-terminal sequence was replaced with that of Xenopus laevis TTR), pigC/crocTTR (crocTTR in which the C-terminal sequence was replaced with that of Sus scrofa TTR), and xenoN/pigC/crocTTR (crocTTR in which the N-and C-terminal sequences were replaced with that of X. laevis TTR and S. scrofa TTR, respectively) were studied and compared. Using either casein or apoAI as a substrate, crocTTR had a lower proteolytic activity than human TTR. Replacing the C-terminal sequence of crocTTR increased the activity (casein: 1008 ± 36 pmol/min; apoAI: 231 ± 43 pmol/min), whereas replacing the N-terminal sequence decreased the activity (casein: 299 ± 26 pmol/min; apoAI: 31.5 ± 2.0 pmol/min). The activity of xenoN/pigC/crocTTR (casein: 502 ± 11 pmol/min; apoAI: 371 ± 23 pmol/min) was higher than those of crocTTR or xenoN/crocTTR, but similar to that of pigC/crocTTR. These results are the first to show the proteolytic activity of reptile TTR, and that the activity is changed when the N-and/or C-terminal amino acid sequences of the TTR subunit are changed.

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Increasing the length and hydrophobicity of the C‐terminal sequence of transthyretin strengthens its binding affinity to retinol binding protein

et al. 2017

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Transthyretin ( TTR ) is a transporter for thyroid hormone ( TH ) and retinol, the latter via binding with retinol binding protein ( RBP ). Both the N‐terminal and C‐terminal regions of the TTR subunit are located in close proximity to the central binding channel for ligands. During the evolution of vertebrates, these regions changed in length and hydropathy. The changes in the N‐terminal sequence were demonstrated to affect the binding affinities for TH s and RBP . Here, the effects of changes in the C‐terminal sequence were determined. Three chimeric TTR s, namely pigC/hu TTR (human TTR with the C‐terminal sequence changed to that of Sus scrofa TTR ), xenoN/pigC/hu TTR (human TTR with the N‐terminal and C‐terminal sequences changed to those of Xenopus laevis and S. scrofa , respectively), and pigC/croc TTR ( Crocodylus porosus TTR with the C‐terminal sequence changed to that of S. scrofa TTR ), were constructed and their binding affinities for human RBP were determined at low TTR / RBP molar ratio using chemiluminescence immunoblotting. The binding dissociation constant ( K d ) values of pigC/hu TTR , xenoN/pigC/hu TTR and pigC/croc TTR were 3.20 ± 0.35, 1.53 ± 0.38 and 0.31 ± 0.04 μ m , respectively, and the K d values of human and C. porosus TTR were 4.92 ± 0.68 and 1.42 ± 0.45 μ m , respectively. These results demonstrate chimeric TTR s bound RBP with a higher strength than wild‐type TTR s, and the changes in the C‐terminal sequence of TTR had a positive effect on its binding affinity for RBP . In addition, changes to the N‐terminal and C‐terminal sequences showed comparable effects on the binding affinity.

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Crocodile transthyretin: structure, function, and evolution

Cited by 31 publications

References 53 publications

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

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

Proteolytic activity of Crocodylus porosus transthyretin protease and role of the terminal polypeptide sequences

Increasing the length and hydrophobicity of the C‐terminal sequence of transthyretin strengthens its binding affinity to retinol binding protein

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