Type II secretion: the substrates that won't go away

Type II secretion systems (T2SSs) generally release their substrates into the culture medium. A few T2SS substrates remain anchored to or bound at the surface of the bacteria after secretion. Since they handle already folded proteins, T2SSs are the best way for bacteria to target, at their surface, proteins containing a cofactor, proteins that have to be folded in the cytoplasm or in the periplasm, or multimeric proteins. However, how a T2SS deals with membrane-anchored proteins is not yet understood. While this type of protein has until now been overlooked, new proteomic approaches will facilitate its identification.