I was surprised to read in Chapter 7 that molecular crowding can help the self-assembly of macromolecules, as I seemed to remember reading that crowding promotes the formation of cytotoxic protein aggregates. After a brief search of the literature it turns out (surprise, surprise) that the issue is somewhat complicated.
It seems that the key factor is the size of the molecules which are doing the crowding. My confusion was due in large part to a clash of terminology. Crowding as described by Ellis and Minton 2006 is problem encountered by protein's as they fold in a cellular medium and is due to the presence of other macromolecules. It has also been suggested that protein chaperones play a key role in abating the effects of crowding on protein folding.
I suspect that the crowding effect described by Nelson and that by Ellis and Minton exist on a continuum, with some cellular constituents providing a "positive" contribution to folding while others are more inhibitory. I would also expect that both effects have a strong dependence on the respective concentrations.
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Ellis, R.J. & Minton, A.P. Protein aggregation in crowded environments. Biol. Chem.
387, 485–497 (2006).
Hmmm... I'm not convinced that Nelson was at any point insinuating that crowding by small molecules helps the self-assembly of correctly-folded macromolecules: it seemed more that any large objects will tend to aggregate and the actual folding of any proteins or similar will then be determined by the size, shape, charge distribution, etc. of whichever macromolecule they end up next to.
ReplyDeleteIs the effect described by Ellis and Minton plain old steric hindrance, or is there more to it than that?
Have a look at paragraphs 2-3 on page 254, while Nelson doesn't explicitly talk about protein folding, he seems to suggest that the presence of a "crowding agent" reduces the entropic component of the free energy associated with self-assembly. Perhaps my extrapolation isn't appropriate.
ReplyDeleteI got the impression that steric hindrance was the major contributor.