This is a very interesting paper which confirms the observations made in a number of previous studies. The structure of the E2 region gives us a much clearer picture of the overall structure of APP. While the structure of a number of regions of the ectodomain have not yet been determined, it is quite likely that these other regions will contain less structure than the N-terminal domain and the E2 domain, which is the subject of the present study.
It was pleasing to see confirmation of our prediction that the E2 domain is structure rich and that it contains a heparin-binding domain (see Mok et al., 1997). The dimerization of APP (although previously demonstrated in vitro) is also important, although it is difficult to reconcile the models shown in Fig. 6A of the paper with the crystal structure of the dimer (Fig. 4A).
The only major concern is whether the unglycosylated structure expressed in E coli will be similar to the native mammalian N-glycosylated structure.
Finally, the idea that the...