Primary sequence domains required for the retention of rotavirus VP7 in the endoplasmic reticulum

The method by which VP7 is retained in the ER is unresolved. Though clearly not a membrane spanning protein, VP7 is membrane bound (13) . The mode of this attachment is not obvious. If an a-helical wheel (32) of the amino acid residues from Q51 at the mature amino terminus to Wl, is constructed, a marked amphipathicity is observed with all the charged residues segregated to one segment of the circumference of the wheel. Such a hydrophobic face may be present in the folded structure and mediate membrane at-tachment. The rotavirus nucleocapsid protein VP6 has been shown to oligomerize (11) and whether or not VP7 oligomerizes is being examined. The possibility exists that an amphipathic character may influence oligomerization and play a role in the membrane association of VP7. The nature of the ER retention of the VP7 is also being investigated and presumably involves some specific sorting feature such that the organelle retains its characteristic components. Such sorting remains an elusive problem for the retention of all types of ER molecules including the integral membrane proteins HMG CoA reductase (19) , ribophorins (33) , signal sequence receptor (40) , ERP99 (20) , adenovirus E3 (26), the lumenal protein of the ER disulfide isomerase esterases (24) , and heavy chain binding protein (4) . With respect to the latter class, 'KDEL', found to be necessary for targeting other proteins, is not a component of VP7 and cannot explain its ER retention. There is no sequence homology with other ER constituents on the primary sequence level although it remains to be determined whether folded structures of ER constituents bear any resemblance to each other.