It's funny, I'd actually created an outline for a timeline with this basic premise a couple months ago (never really got past the planning stages unfortunately), so I have a couple of thoughts.
Firstly, if the King dies, we're probably going to see a major backlash against the Jewish community in Lisbon. OTL, there was almost mass mobbing and murders against them, so it's likely that in this situation, that escalates into at least a few murders. It'd be up to the writer to decide how far that goes, but I know in my timeline it would have led to a ban on Jewish people in the city for at least a decade following, due to public prejudice.
You might also not see the Ribeira Palace rebuilt. OTL, the King just fixed it back to being a monument to Manuel I, but here, it's potentially where a King, the new King's brother, died tragically. There might be a move back to the traditional Palace of Alcáçova, which didn't fall, although it did get damaged in the earthquake. It would depend on (a) if that's where the royal family died, and (b) how much Luis can standing living where his brother was killed. It'll probably be rebuilt in the end, but you might see the Palace of Alcáçova getting a second chance as the royal centre, at least until the stigma of Ribeira wears off. Remember, it's only been the chief royal residence for less than 30 years, so its more likely to be left behind.
As to Luis I of Portugal's bride, I think he'll push hard for Mary Tudor, but it's unlikely they'll end up married. He'll refuse to take her without confirmation of her legitimacy at the bare minimum, and Henry VIII is not a man to change his mind for ease and comfort. I'd say Luis will give up around the 1540's, and you'll see him maybe try for a German, Italian or French bride. Marie of Guise will be a widow by the mid 1540's, with a proven track record of successful childbirths, although I doubt she'll bite. But she had sisters, and there were other families who'd love to see their daughters as Queen of Portugal. Jeanne d'Albret is a potential and interesting choice. Hell, I could even see Amalia of Cleves as Queen in the right circumstances, and had her as my top pick when outlining my timeline. If Marguerite of France hasn't been snapped up as Philip, Prince of Asturias' bride, she'll also be a top contender.
I'm strongly for a marriage in the 1540's, because that's when Luis OTL lost his two youngest brothers with wives and children, which ITL is the loss of the two potential lines of succession. If the Duke of Guarda also is dead, and considering his death was most likely a household illness that took his entire family that's possible, then I can see Luis rushing to marry if just because suddenly the Aviz line is a lot flimsier than previously thought.
Those are my basic thoughts, and bare in mind a lot of these were based off about three hours of research when trying to come up with a timeline that didn't happen (although I'm going to go back and give it a good look over to see if it might work now) but I think I've made a couple of decent points.