The majority part of a protein is unstructured (as per the Alphafold model) and just the part that has been seen to bind to a certain component is structured so far. When the protein binds to this component, it forms a homodimer. Can I fix this complex and elucidate the structure of the entire protein via X-ray crystallography?
Beceaus part of the protein is unstructured, you cannot solve its structure, since it does not have any. Of course, if part of the protein gets structure, like uppon binding to a partner in your case, in principle that part of structure can be solved. For crystallography, you probably want to work with constructs, which contain only the parts which are getting structure.
However, there are many techniques, which can help you with some characterization of disordered proteins: circular dichroism (CD) can give percentaes of ordered and unrdered regions; chemical crosslinking with mass spectrometry can tell you if certein pars gets preferentially close to each other; small angle X-ray scattering can give you size distribution, general idea on flopiness e.g. if the protein is really disordered, confirm the atomic models (e.g. if you go for MX, you can check if various trimings actually give you compact particle, before you go for crystallization) etc.
Btw., we provide access to many of these techniques via European research infractructures (Instruct, MOSBRI)
Solving the structure of a protein that is mostly unstructured can be challenging, but it's not impossible. Here's a general approach you could consider:
Identify Structured Regions: Since you mentioned that only the part of the protein involved in binding to a specific component is structured, start by identifying and characterizing this structured region. This might involve experimental techniques such as X-ray crystallography, NMR spectroscopy, or cryo-electron microscopy (cryo-EM).
Construct a Model: Using the known structure of the structured region, along with computational modeling techniques, try to construct a model of the entire protein. This could involve methods like comparative modeling (using known structures of homologous proteins), threading (comparing the protein sequence to known structures to predict its structure), or molecular dynamics simulations.
Experimental Validation: Once you have a model of the entire protein, validate it experimentally. This could involve techniques like small-angle X-ray scattering (SAXS) to characterize the overall shape and dimensions of the protein or hydrogen-deuterium exchange mass spectrometry (HDX-MS) to probe its dynamics and folding.
Complex Formation and Crystallization: If the protein forms a homodimer when binding to its component, you could try to form and crystallize this complex. This could potentially provide additional structural information about the unstructured regions of the protein, especially if they become ordered upon binding.
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