In contrast to the block in production of H244A VLP, the H244A DI/II protein was efficiently secreted from cells. Mutant protein secretion was somewhat reduced, with the final yield of DI/II H244A about half that of the WT protein in two separate preparations (data not shown), suggesting some effects of nonoptimal pr interaction. However, unlike the E protein in virus or VLP, the truncated DI/II protein lacks the TM region and does not mediate membrane fusion, and thus may be relatively independent of the pH-protection function of pr. The purified WT and mutant DI/II proteins were able to bind liposomes and form core trimers that were stabilized by DIII (Fig. 6) . Thus, the mutant protein is correctly folded and active in membrane insertion. Studies with conformation-specific mAbs also provided evidence for the correct folding of H244A E protein (Fig. 8B) . Together, these results suggest that the H244A E protein is still able to access the chaperone functions of prM, while its decreased pr binding indicates that it can no longer utilize the pH protection functions of pr.