Transcripts
DR. LINGWOOD:
Okay, this figure is, again
another format of the receptor Globotriaosyl
ceramide, and you can see here the three sugars.
See, I've told you that the last
two, the galactose alpha one-four beta one-four galactose structure is a
recognition unit. But this is a very interesting
system and is telling us a lot about how the
proteins interact with these types of
carbohydrates in general, which is one of the
reasons why I'm so interested in it. Although
the toxin binds in this area, if you remove
this, you clip Gb3 in half here and you lose
this lipid part, then there's no receptor
activity.
So somehow the part that's in
the cell membrane affects the ability to bind.
And it's not only the structure of the lipid
that affects binding, but when it's in a
membrane you can imagine lots of other
hydrophobic structures here which would be the
plane of the membrane that also affect the
ability of the toxin to bind, here. So this is
an incredibly dynamic situation.
People had thought before that
this kind of interaction was just the toxin
binding to the sugars and that's it, but it's
not. There's an incredible amount of modulation
of affinity. And we don't really know what is
going on in terms of molecular structure, here.
But we have a few ideas and they are
revolutionizing the way we think about the
ability of proteins to bind to carbohydrate when
it's on a cell surface.
And that effect is that because
it's such a complex situation, there's such a
lot of influence on whether the actual toxin can
bind here, that these kinds of structures, the
lipid structure, the membrane environment all
become, if you like, risk factor for HUS because
they play an important role in determining
whether the toxin can bind cells.
And as I will show you later,
even that's only half the story because once the
toxin has bound, it has to get inside the cell
to kill the cell and that, again, is a variable
system. There are several choices. And the
choices, again, seem to be related to the lipid
structure rather than the carbohydrate of Gb3.
