Why does pH denature proteins?

Ben Davis bjd12 at cus.cam.ac.uk
Mon Sep 5 02:06:42 EST 1994

Louis Hom (lhom at OCF.Berkeley.EDU) wrote:
: Why do extremes in pH lead to protein denaturation?

	Couple of general points, then a funny example that I've been working

	Just thinking about low pH (which is what I'm more used to), what 
tends to happen is that you protonate the vacrious acidic groups in the 
protein, and eventually, this destablises the protein sufficiently to unfold
it. In the case of barnase, this happens when you protonate the acidic partner
of a buried salt bridge - the energetic cost of having a buried lone charge is
too destablising, and the protein unfolds. As far as I can tell, this is
fairly typical, in that one crucial event causes the protein to unfold.

	The protein that I've been working on, barley CI-2, is different, in
that the lowest pKa is 2.7, but the protein is folded to at least pH 2.2 - in
other words, there is no titrating sidechain that causes the protein to 
unfold.One possible explanation may be backbone titration (amide group has 
pKa of ~-1, so at pH 1 1% of the groups will be protonated, which may be 
enough to tip the protein to being unfolded), or it may be the increased salt
at lower pH (the acid denatured state is very sensitive to salt 

: *   Lou Hom			*	"All folks are family."            *
: *   lhom at ocf.berkeley.edu       *    			-- John Saponara   * 



Ben Davis,
MRC Protein Function and Design,
Cambridge, UK

"They can make me do it, but they can't make me do it with dignity."

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