FIG. 4.

Models of GP-mediated fusion. (A) In our model, initial cleavage of GP1 (by CatB, CatL, or other proteases) removes the mucin-like domain generating a 50-kDa species (not shown). This 50-kDa species is then primed by CatB plus CatL (or another protease) cleavage of GP1 to produce 20-kDa (royal blue) and then 19-kDa (purple) forms of the glycoprotein. This primed form of GP is then acted upon by an additional cellular factor, such as a lysosomal thiol reductase, which reduces a critical disulfide bond, possibly the disulfide bond between GP1 and GP2. This reduction relieves the GP1 clamp, thus allowing conformational changes in GP2 that expose and reposition the fusion peptide (red arrowhead) and trigger fusion. (B) In the model proposed by Chandran et al. (2), initial cleavages by CatB and/or CatL generate an 18-kDa GP1 intermediate (royal blue, which we hypothesize is equivalent to our 20-kDa intermediate with one N-linked glycosylation site removed). Further cleavage by CatB completely digests GP1, thereby removing the clamp and allowing fusion. N-linked glycosylation sites in GP1 are depicted with short branched black lines.