Yes it is definitely possible to crystallize a protein that is insoluble and makiing inclusion bodies. If it is a membrane proteins, then you have to optimize protein folding in presence of detergents and accurate buffer compositions. Membrane proteins are difficult to crystallize but there are special kits for screening of membrane proteins available in Molecular Dimensions, Qiagen, sigma etc.. If it is not a membrane protein and making inclusion bodies then you have to refold protein by dialysis. But ofcourse each protein have different characteristics, such as-

- how many disulphide bods are there in structure? use DTT if it is the case.

-Size of protein, e.g. large molecular weight protein are difficult to refold than small one!

-your choice of expression system, e.g. if a protein is periplasmic or, membrane. sometimes the expression is better, if you have periplasmic signal with you protein for transport.

- if it is a membrane protein you have to be ready to refold and detergent optimization.

It is definitely possible to crystallize proteins which are insoluble and produced as inclusion bodies. Infact there is no additional difficulties for crystallizing such proteins. The only challenge is to refold the protein.

There are several methods of refolding, like using buffer dilution, refolding column (you could found a loads on them just by searching in google)

I have listed some of them,

http://structbio.vanderbilt.edu/chazin/wisdom/labpro/inclusion.html

It is definitely possible to crystallize proteins which are insoluble and produced as inclusion bodies. Infact there is no additional difficulties for crystallizing such proteins. The only challenge is to refold the protein.

There are several methods of refolding, like using buffer dilution, refolding column (you could found a loads on them just by searching in google)

I have listed some of them,

http://structbio.vanderbilt.edu/chazin/wisdom/labpro/inclusion.html

http://onlinelibrary.wiley.com/doi/10.1002/9780470939932.ch13/summary

http://www.embl.de/pepcore/pepcore_services/protein_purification/extraction_clarification/invitro_denaturation_refolding/

Once you could be able to refold the protein, it would be as good as normal soluble protein in terms of crystallization.

Best of luck.

Dear Govindan,

I dont know why my comments dissapeared. I add my reply again here.

Yes it is definitely possible to crystallize a protein that makes inclusion. there are many proteins that can make inclusion, even if they are not membrane proteins. If your protein is membrane anchoring then may be you can try to crystallize only soluble part by deleting membrane anchor. But, if ti is a membrane spanning then you have to use detergent during refolding process. there are many detergents you can read about them in reviews, e.g. cationic, anionic and zwitterionic. you can select the best one known to used for protein refolding. Then you need to optimise buffer and salt conditions for maximum solubility that will also favour to concentrate your protein solution. some times if your protein is membrane anchor or periplasmic then you can add signal peptide with your protein to transport that helps in folding.

There are several approach for refolding, e.g. you can use dilution method for it.there are several kits available from Molecular dimension and qiagen specially for membrane proteins. you can try them for getting crystallization condition for your protein. remember, if proteins are smaller in size, they can refold better than extremely lagre one.

Each potein has different nature so its just a trial and hit approach to get best crystallizing condition for any protein. However there are some strict parameters that crystallographers follows.

1. your protein should be homogenous, e.g. represent one oligomeric conditions (you can see it by DLS).

2. after purification last purification should be in gel filtration. try to purify as much as possible.

3. concentrate protein as much as possible (at least between 8-20 mg/ml).

4. Use maximum screens to find the exact crystallizing conditions.

5. some times temperature during incubation of crystal plates is also considered, such as 25 degrees or 4 degrees.