Transthyretin modeling

Figure 14.8 Proposed model of p sheet helix of the fibrous form of transthyretin. The repeating unit of the P helix comprises 24 P strands with an average twist of 15° between each strand giving a complete turn of 360°. Four transthyretin polypeptide chains contribute to the repeat unit and are shown here in different colors. (Adapted from C. Blake and L. Serpell, Structure 4 989-998, 1996.)...

Cardoso, I., Goldsbury, C. S., Muller, S. A., Olivieri, V., Wirtz, S., Damas, A. M., Aebi, U., and Saraiva, M. J. (2002). Transthyretin fibrillogenesis entails the assembly of monomers A molecular model for in vitro assembled transthyretin amyloid-like fibrils./. Mol. Biol. 317, 683-695. 

A. Type I—Direct-Stacking Models Transthyretin and Superoxide Dismutase... 

Meerts lA, van Zanden JJ, Luijks EA, van Leeuwen-Bol I, Marsh G, Jakobsson E, Bergman A, Brouwer A (2000) Potent competitive interaction of some brominated flame retardants and related compounds with human transthyretin in vitro. Toxicol Sci 56 95-104 Mengel K (1985) Dynamics and availability of major nutrients in soils. Adv Soil Sci 2 67-134 Mercer JW, Cohen RM (1990) A review of immiscible fluids in the subsurface Properties, models, characterization, and remediation. J Contam Hydrol 6 107-163 Mertens JA (2000) Trichloroethylene. In Kirk-Othmer Encyclopedia of Chemical Technology. Wiley New York. Available at http //www.mrw.interscience.wiley.com/emrw/9780471238966/ kirk/article/tricmert.aOl/current/pdf... 

A possible explanation for the highly selective retention of the OH-PCBs in blood may be their structural resemblance with thyroxin. Both rats and mice metabolize PCB 77 by CYPIA to the 1,2-shift metabolite, 4-OH-3,5,3, 4 -PCB, 5-OH 3,3, 4,4 -PCB, and 6-OH-3,3, 4,4 -PCB (McKinley et al. 1993 Morse et al. 1995). Only the 4-OH metabolite was selectively retained, with blood containing 4-OH-3,5,3, 4 -PCB at a concentration 15 times higher than the parent compound, 5 days after oral exposure to PCB 77 in mice (Bergman et al. 1994). This metabolite was found to be bound to a thyroxin-transporting protein (transthyretin) in the blood (Brouwer et al. 1986). Competitive binding studies of OH-PCBs relative to T4 and computer modeling showed that OH-PCBs with the substituents in meta or para positions were much more effective competitors for T4 than if the substituents were bound in an ortho position (Rickenbacher et al. 1986). 

A study of the tetrameric transthyretin (TTR) complex by means of TWIM-MS, computational modeling, and activation of selected ions by acceleration in the source region of the instrument, revealed that during the dissociation of protein complexes a number of partially-folded intermediate states were stable during the time-scale of the experiment (5-25 ms) [75], The results indicated that upon activation, unfolding of one or more subunits occurred while the remainder of the subunits remained folded. This occasion was the first time that partially-folded intermediates had been studied such types of measurements will allow future studies into the understanding of the dissociation mechanism of other large protein complexes to be carried out. 

Figure 4 Model of atRA biogeneration in mammals. REH, retinyl ester hydrolase (e.g., ES4 and ES10) TTR, transthyretin RAR-RXR, the heterodimer of retinoic acid receptors with retinoid X receptors atRCHO, all-frans-relinal atROH, all-frans-retinol CRBP(I), cellular retinol binding protein, type I LRAT, lecithin retinol acyltransferase SRBP, semm retinol binding protein. CRBP(I), CRABP(I), and CRABP(II) have been placed in the same cell for simplicity. This does not necessarily occur in vivo.

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