It seems that there are eukaryotes that can live above 45 C. There is a nice review article life in extreme environments that has charts out the upper temperature limits for each taxa, at least as known in 2001. This paper claims ~60 $^o$C and a different paper without a reference for it claimed the world record was 62$^o$C. So it seems that even with real organisms there may be a little more wiggle room for higher temperatures for your story purposes.
reducing chemolithoautotroph, capable of growing at the highest temperatures of up to 113 $^o$C (ref. 15). Hyperthermophile enzymes can have an even higher temperature optimum; for example, activity up to 142 $^o$C for amylopullulanase 16. There are thermophiles among the phototrophic bacteria (cyanobacteria, purple and green bacteria), eubacteria (Bacillus, Clostridium, Thiobacillus, Desulfotomaculum, Thermus, lactic acid bacteria, actinomycetes, spirochetes and numerous other genera) and the archaea (Pyrococcus, Thermococcus, Thermoplasma, Sulfolobus and the methanogens). In contrast, the upper limit for eukaryotes is ~60 $^o$C, a temperature suitable for some protozoa, algae and fungi. The maximum temperature for mosses is lower by another 10 $^o$C, for vascular plants it is about 48 $^o$C, and for fish it is 40 $^o$C, possibly owing to the low solubility of oxygen at high temperatures (Fig. 3
3).
I think the bottom up approach to adaptations, is interesting. But it seems like there are adaptations before a sharp temperature cut off. For example, DNA denatures in the lab ~ 95 $^o$C when doing PCR. I would have assumed that would be a hard cutoff, but apparently DNA in a hyperthemophile grows optimally at 100$^o$C. So the conditions inside the cell are more important than the stability of the molecule in isolation.
It seems that after cell membranes that the flexibility and stability of proteins is probably really important. I think the protein structures would need to be stiffer and less floppy at higher temperatures.
If I read you original goal correctly, the goal was to have a large animal and you wanted to avoid overheating in the center of the animal. Making the cells survivable to temperature I think is one thing, but another think to think about is how oxygen gets transported to the cell. I think with increased temperature that oxygen binding to hemoglobin decreases. Also in general the percentage disolved gasses in a fluid decreases with increased temperature. 279