Wouldn't a HSQC of 15N-labeled protein be a relatively easy yes/no
experiment? Maybe it would not be incredibly definitive?

Jacob


On Mon, Dec 6, 2010 at 11:10 AM, Mischa Machius <[email protected]> wrote:

> Daniel,
>
> You'll probably have to monitor pH changes through size changes of your
> protein, provided the structural changes will indeed cause size changes.
>
> You said "easy", so that probably rules out Small-Angle X-Ray Scattering
> (SAXS), but that would be the highest-resolution method. You can try static
> and dynamic light scattering, analytical ultracentrifugation and
> fluorescence anisotropy. If you are really lucky, size exclusion
> chromatography might work too.
>
> And then there are the "difficult" ways...
>
> MM
>
>
>
>
> On Dec 6, 2010, at 11:59 AM, Daniel Jin wrote:
>
> Dear CCP4 colleagues,
>
>
>
> We have a protein that is composed of two domains connected by a short
> peptide linker. We have some indirect evidence showing that the two domains
> may somehow move against each other when exposed to different pH. It is
> unlikely to have any obvious secondary structure change since each domain
> behaves like a rigid body. I am wondering whether there is any “easy” way,
> biochemically or biophysically, to monitor the conformational changes in
> solution. Many thanks.
>
>
>
> As far as I know most of the pH sensing stories are linked to histidine
> residue. Can you point me to any references that show a different pH sensing
> mechanism (other than His)? Thanks.
>
>
>
> Best,
>
> Daniel
>
>
> -----------------------------------------------------------------------
> Mischa Machius, PhD
> Director, Center for Structural Biology
> Assoc. Professor, Dept. of Pharmacology
> Member, Lineberger Comprehensive Cancer Center
> University of North Carolina
> 4079 Genetic Medicine
> CB#7365
> 120 Mason Farm Road
> Chapel Hill, NC 27599-7365, U.S.A.
> tel: +1-919-843-4485
> fax: +1-919-966-5640
> email: [email protected] <[email protected]>
>
>


-- 
*******************************************
Jacob Pearson Keller
Northwestern University
Medical Scientist Training Program
cel: 773.608.9185
email: [email protected]
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