Hello Marek, 182 kDa protein is nothing special - unless it has huge areas of disorder, membrane-association domains, coiled coils, or something like that. Much larger proteins and protein complexes have been successfully crystallized.
With respect to purification - this is where you may want to diversify. There are numerous avenues open to you: you can explore other forms of distributive chromatography (HIC, IE, etc.); you can opt to use other affinity matrices (dye resins, etc.) or you can try sizing using a non-carbohydrate matrix. Not to mention that there are numerous options for IMAC - Ni-NTA is just one of many. I would be glad to help you further off the main list if you want to share more details. Cheers, Artem
