Fc fusion protein smearing on SDS PAGE - (Aug/18/2011 )

I have several Fc fusion proteins that when I run non-reduced on sds-page (nupage gel) I see a smear from where the protein band would be if it was reduced up to the non reduced molecular weight. Do you know what would be causing this? The sample is not in any reducing conditions. Thanks!

you may be experiencing some dissociation caused by the presence of sds.

If you are using the invitrogen precast gels they recommend using their Tris-glycine native running buffer. The recipe for it would be the same as your standard TGS, just omit the SDS.