Dear all,

I am posting a summary of How to avoid protein trafficking to Inclusion
body???

My question was  "What can be done to avoid a protein going inside inclusion
body?The gene is cloned in pET30a with C-ter his tag and  expressed in
BL21-DE3 from 37 to 18C for 3-4 hr with .5mM of IPTG,it is going to
inclusion body."

Shivesh



David Cobessi  wrote,
I do not know which kind of protein it is or the pET30a characteristics.
But...
You could first not add IPTG and see if the gene is expressed. It
happens often.
You could also decrease more the IPTG concentration.
You could also clone the gene with the His-tag in Nter instead of Cter.
You could also change the expression system.
Good luck,
David
--
David Cobessi, PhD
UMR7175-LC1, Institut Gilbert-Laustriat
Ecole Superieure de Biotechnologie de Strasbourg
Departement Recepteurs et Proteines Membranaires
Boulevard Sebastien Brandt
BP 10413
67412 Illkirch Cedex
France
Tel 33 (0)3 90 24 47 47
   33 (0)6 08 16 43 40
Fax 33 (0)3 90 24 48 29
http://recepteurs.u-strasbg.fr
http://site.voila.fr/d.cobessi







Brenda Patterson wrote



Lower temperature, use chaperones (e.g. TAKARA set), refolding?



Mohinder Pal wrote
I had the similar problems with the protein expression but I tried heat
shock at 42 degree C for 25 mins before induction with IPTG and
 approximately 60% of the overexpressed protein become soluble. The
explanation for this is the upregulation of heat shock proteins that may
help in the refolding of the overexpressed proteins. So it is woth to try.

Best of luck.

Mohinder

---------------------------------------------------------------------------------
Mohinder Pal
Ph.D Student
Protein Crystallography Group
School of Biological Sciences
University of Southampton
Bassett Crescent East
Southampton
SO16 7PX UK
[EMAIL PROTECTED] <mailto:[EMAIL PROTECTED]>
Fax: +44 (0)23 8059 4459



Also worth trying a lower IPTG level ~ 0.1mM and or different media, e.g.
TB, SOC or m9 instead of LB, it's all a bit random but sometimes these
things can make a difference.  Adding 3% EtOH on induction worked for me
once, it's supposed to shock the cells and stimulate chaperone production, I
was surprised I must say.  Funny old world......



Giles Robertson D.Phil.
[EMAIL PROTECTED]
Tel: 02076316813

School of Crystallography,
Birkbeck College,
University of London,
Malet Street,
London, WC1E 7HX.

-

Peter J. Miller wrote


On 2 Apr 2008, at 12:19, Brenda Patterson wrote:

Lower temperature, use chaperones (e.g. TAKARA set), refolding?


Quoting shivesh kumar <[EMAIL PROTECTED]>:

Dear all,
Sorry for the off-topic question...
What can be done to avoid a protein going inside inclusion body.The gene is
cloned in pET30a with C-ter his tag and  expressed in BL21-DE3 from 37 to
18C for 3-4 hr with .5mM of IPTG,it is going to inclusion body.All
suggestions are welcome.
Thanx in advance.
Shivesh

Is there any reason that it has to be expressed solubly?  Why not let it go
into inclusion bodies and then refold it.  That is what we do with most of
our proteins...works great.

Peter

Peter J. Miller
Collins Laboratory
Department of Biochemistry and Biophysics
University of North Carolina at Chapel Hill
919-966-9410



Louise Major wrote


My favourite media is TPB - (paper is: Moore et al Protein expression and
purification (1993) 4: 160-163).  I've had luck with this and BL21 (DE3)
Gold cells.  I'm also a fan of cold shocking cells - after initial growth at
37 deg C, put flasks in an ice water bath for 10 min, then add IPTG and
tranfer to 16-25 deg C for expression.   This combination rescued a protein
that behaved like ball bearings in all other conditions.  It always seems
worth trying an array of strains vs an array of media vs cold shock/heat
shock/chaperones, and a bit of tweaking of [IPTG]

Good luck,
Lou

- Show quoted text -



At 11:06 02/04/2008, you wrote:

Dear all,
Sorry for the off-topic question...
What can be done to avoid a protein going inside inclusion body.The gene is
cloned in pET30a with C-ter his tag and  expressed in BL21-DE3 from 37 to
18C for 3-4 hr with .5mM of IPTG,it is going to inclusion body.All
suggestions are welcome.
Thanx in advance.
Shivesh



********************************************************
Louise Major
Centre for Biomolecular Sciences
North Haugh
The University
St Andrews
Fife KY16 9ST
Scotland



Guentet wrote

if you try to express a disulfide containing protein use Origami strains
(Novagen) and keep temperature below 25 °C.
Induction of chaperones as mentioned already is often very effective or
co-expression of chaperones:

de Marco, Deuerling et al. BMC Biotechnol. 2007; 7: 32. 2007
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17565681

Godd luck,

Guenter

Priv.Doz.Dr. Guenter Fritz
Fachbereich Biologie
Sektion Naturwissenschaften
Universitaet Konstanz
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