Hi Jacob -
Sorry if I caused any misunderstanding, but I am not saying that kD is
not mattering in cells.
Of course it should matter.
I am making the distinction that the concentration dependent component
of it, k(on), is of less
importance, since in the viscous environment of a cell, the chance of
two molecules to find each other
should be limited by diffusion rates before concentration becomes the
limiting factor for their chance
to meet and form a complex.
The concentration independent component of kD, k(off), the half time
that two molecules need
to break a complex once formed, I think is what is most relevant in
the cell.
Although I came across this argument a few times, and I find it
convincing, I am not aware of a paper
that proves the first derivation, that indeed diffusion rates will be
the limiting factor. Unless someone
posts the reference, I just got myself an evening project to find it ...
A.
On Jul 5, 2010, at 0:18, Jacob Keller wrote:
4. The physiological concentration is a bit misleading. First, its
clear
now that cells have microenvironments,
and 'physiological' concentrations are hard to define. Also, in a
cell, I
think (and I think others tend to agree)
that kD plays little role at the end. kD is a combination of k(on) -
which is concentration dependent but in a cell
very likely diffusion limited - and of k(off) which I think is what
matters most in the cell.
Can you provide some references about kD not mattering in cells? I had
thought it a basic tenet that kD was a major indication of
physiological
relevence. After all, one could presumably determine a kD for any two
proteins, so the order of magnitude of the kD would seem to matter.
I hear
that your argument is more subtle in considering the elements of kD,
but
isn't kD usually a rough indicator of k(off), and of course more
readily-accessible experimentally? I am intrigued by the idea...
Jacob Keller
P please don't print this e-mail unless you really need to
Anastassis (Tassos) Perrakis, Principal Investigator / Staff Member
Department of Biochemistry (B8)
Netherlands Cancer Institute,
Dept. B8, 1066 CX Amsterdam, The Netherlands
Tel: +31 20 512 1951 Fax: +31 20 512 1954 Mobile / SMS: +31 6 28 597791
