PARL blocking peptide

To clarify the effect of asymptomatic carrier trees on the epidemic spread of pine wilt disease, we inoculated Bursaphelenchus xylophilus (Steiner and Buhrer) Nickle into similar to 10-year-old Pinus thunbergii Parl. trees to make asymptomatic carrier trees of the nematodes, and then we examined the relationship between pine wilt disease development in these trees and their use by Monochamus alternatus Hope. Mature adults of M. alternatus were attracted by and oviposited on trees that died in summer and fall, regardless of whether they died in the year of nematode infection or were asymptomatic during the infection year and died the next year. These results suggest that trees that die in summer and fall should be disposed of to help control M. alternatus and limit epidemic spread of the disease. In addition, we suggest the possibility that M. alternatus larvae may not grow and develop in trees that die after the infection year or that M. alternatus adults that emerge from such trees do not carry many B. xylophilus.

The mitochondrial rhomboid protease Parl governs apoptosis, morphology, metabolism and might be implicated in Parkinson's disease, but the structural basis of its activity and complex regulation remain unknown. We report the discovery of c-cleavage, a proteolytic event on the loop connecting the first transmembrane helix (TMH) of Parl to the 6-TMH catalytic rhomboid domain of the protease. This cleavage disrupts the '1+6' structure that defines every mitochondrial rhomboid and generates a new form of Parl, PROD (Parl-rhomboid-domain). Structure-function analysis of Parl suggests that c-cleavage could be implicated in eliminating Parl proteolytic activity, and structural modeling of PROD reveals structural conservation with the bacterial rhomboid GlpG. However, unlike bacterial rhomboids, which employ a diad-based mechanism of catalysis, Parl appears to use a conserved mitochondrial rhomboid-specific Asp residue on TMH-5 in a triad-based mechanism of catalysis. This work provides unexpected insights into the structural determinants regulating Parl stability and activity in vivo, and reveals a complex cascade of proteolytic events controlling the function of the protease in the mitochondrion. Cell Death and Differentiation (2011) 18, 1531-1539; doi:10.1038/cdd.2011.22; published online 18 March 2011