Transcripts
DR. LINGWOOD:
What we've done here is to take
that lipid structure off the Gb3. Do you
remember the two chains that are embedded in the
membrane? We chopped one off and replaced it
with fatty acid chains of different lengths.
And this is just a carbon number here from 12
through to 24 and, well, there's two different
colors corresponding to the saturated and
unsaturated forms.
What you see is if you have
short 12 carbons or 14 carbons then there's
no binding of VT1. As you increase the carbon
number beyond 16, then there's increased binding.
It reaches a maximum and then falls again as you
go up to C24.
So that means the carbon chain
lengths have an effect on the ability of VT1 to
bind Gb3. If you look at VT2 the profile is
quite different. Actually, this is VT2c, which
is a homologue of VT2, but again, the short
chain species do not work. But really only the
C18 structure with 18 carbons works - you lose
the activity as you increase the chain lengths.
So although these two toxins
bind to the same sugar, they prefer different
lipid structure. They don't bind to the lipid
structure. Lipid isn't involved in the direct
binding but by changing the galactose alpha one-
four galactose presentation, these kind of Gb3
homologues, which have different acid chain
lengths actually exist on your cells.
So when you talk about Gb3, the
sugar part is constant, but the lipid part is
highly variable. And so that then is a risk
factor, if there is a genetic predisposition,
for example, to make more C18 than Gb3 than
somebody else.
