Problem:

I know that in vivo there are a lot fewer transmembranous proteins in general, and that they are produced at a lower rate than their free counterparts. This is mainly because transmembrane proteins are only required in a 2D space on the membrane rather than a 3D cytoplasmic or extracellular space. This (again, very broadly speaking) means that the probability they will interact with their target is higher.

I also know that this is one of the reasons that producing crystals for X-ray crystallography is notoriously difficult for transmembrane proteins.

Required:

Question 1: What are the other reasons that make transmembrane proteins typically tough crystallisation candidates?

Question 2:What specific part of the crystallisation process yields such poor success rates of transmembrane protein structure elucidation?

Please provide discription of all the answers.