A review on the salt bridge ASP177-ARG163 (O-N) of wild-type rabbit prion protein.

Prion diseases are invariably fatal and highly infectious neurodegenerative diseases that affect a wide variety of mammalian species such as sheep and goats, cattle, deer, elks, humans and mice etc., but rabbits have a low susceptibility to be infected by prion diseases with respect to other species. The stability of rabbit prion protein is due to its highly ordered β2-α2 loop (PLoS One 5(10) e13273 (2010); Journal of Biological Chemistry 285(41) 31682-31693 (2010)) and a hydrophobic staple helix-capping motif (PNAS 107(46) 19808-19813 (2010); PLoS One 8 (5) e63047 (2013)). The β2-α2 loop and the tail of Helix 3 it interacts with have been a focus in prion protein structure studies. For this loop we found a salt bridge linkage ASP177-ARG163 (O-N) (Journal of Theoretical Biology 342 (7 February 2014) 70-82 (2014)). Some scientists said on the 2FJ3.pdb NMR file of the rabbit prion protein, the distance of ASP177-ARG163 (O-N) gives the salt bridge of about 10 Å which is nearly null in terms of energy and such a salt bridge is not observed in their work. But, from the 3O79.pdb X-ray file of the rabbit prion protein, we can clearly observe this salt bridge. This article analyses the NMR and X-ray structures and gives an answer to the above question: the salt bridge presents at pH 6.5 in the X-ray structure is simply gone at pH 4.5 in the NMR structure is simply due to the different pH values that impact electrostatics at the salt bridge and hence also impact the structures. Moreover, some molecular dynamics simulation results of the X-ray structure are reported in this article to reveal the secrets of the structural stability of rabbit prion protein.