Is it more or less difficult to find commercially available

Is it more or less difficult to find commercially available antibodies for immunopreciptiation (that work) than antibodies for western blots? Be sure to include a comparison of immunoprecipitation, western blotting, and native western blotting. Consider the the orientation, geometry, physical limitations that each method could possess.

Solution

Western blotting (WB) is widely used to analyze specific protein expression in cell or tissue extracts, and immunoprecipitation (IP) is employed to enrich a specific protein or protein complex from a heterogeneous cell or tissue extract.

It is commercially difficult to find antibodies for IP that work. For IP, you typically need an antibody that recognizes the target protein in its native fold. In western blot antibodies work on completely denatured proteins. In its native fold, the epitope your antibody is recognizing may be sterically obscured (if the antibody was merely raised against a short peptide sequence). Hence, many antibodies that work great for Western blotting do not work for IP.

If the protein of interest is part of a large five member complex, as you say, it is possible that one of those five members might bind your target protein exactly or very close to where your antibody binds its epitope. Thus, again, access to this epitope might be sterically blocked and your antibody might not work. In contrast, in Western blotting the target protein is typically completely denatured (due to the SDS). Thus, antibodies raised against a short peptide should recognize their (denatured) target protein, even if that short peptide is not accessible as long as the protein is natively folded. However, many antibodies are not raised against short peptide sequences but against folded protein. Since SDS-PAGE denatures the protein, these antibodies will then not work for Western blotting (but may work for IP as well, depending on the sequence).