on- and off-rate of antibodies

ChenHA hzhen at freeuk.com
Thu Feb 3 18:53:05 EST 2000


Dima Klenchin wrote::

> I am no expert in this field so I did not know it. Is this really true?
> What distances are we talking about?

Oh dear, I don't have the papers with me, but if you do a search for Schreiber and
Fersht (Nature Structure Biology) or electrostatic steering, you should be able to
find something. I would assume it's a distance of 7-15 Angstrom (but don't quote me
on that).

> _Very_ simplistic - and I perfectly realize that. This geometrical
> correction is pure formalism, in which, upon calculations, all other
> contributing factors are included. Much like the Stokes radius.
> Makes a lot of sense mainly because we usually have no idea
> about relative contribution of all the possible factors.
>
> :Many interactions would lie in a limited
> : range (~ 10^5-10^6
> :M-1 s-1 I think),
>
> Yes, my point was exactly this. On rates of probably >90% of all
> bilogical interactions will be within a single order of magnitude.

I can't give a figure though I very much doubt it's >90%,  That's because the
on-rates can be higher or lower due to a number of factors.   I worked on one
protein that has a lower on-rate, indicating that the collision does not always
produce binding.

> :but some have on-rate which is close to the diffusion limit
> : (~10^9)
>
> That's for ions. Drop it one order for proteins.
>
> :this is due to this 'mysterious force' you mentioned.  A few have on-rates
> : which exceed the
> :diffusion limit (such as the lac operator-lac repressor protein-DNA
> : interaction) which may be
> :due to electrostatic interactions or other unusual mechanisms.
> :
> Wow! I did not know such thing exist! Really? How come? Do they
> behave like strong magnets or what?

Sort of.  Magnet would be a good analogy of basically how long-range electrostatic
steering works.  The positive charges on one attracts or steers the negative charges
of another protein onto the binding sites and vice versa.  The barnase-barstar
interaction is a classic example, and the on-rate can reach 10^10.  This is much
higher than the theoretical on-rate for any protein-protein interaction (which I
think is 10^5).  For some protein-DNA interactions it may be higher, some
suggestions include the sliding of the protein along DNA or hopping of the protein
from one site to another.


>
>         - Dima





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