Importance of extended protease substrate recognition motifs in steering BNIP-2 cleavage by human and mouse granzymes B

Conclusions:
Despite their high sequence similarity, and previously explained by their distinct tetrapeptide specificities observed, the substrate repertoires of mouse and human granzymes B only partially overlap. Here, we show that the substrate sequence context beyond the P4-P1 positions can influence orthologous granzyme B cleavage efficiencies to an unmatched extent. More specifically, in BNIP-2, the identical and hGrB optimal IEAD tetrapeptide substrate motif is targeted highly efficiently by mGrB, while this tetrapeptide motif is refractory towards mGrB cleavage in Bid.

Source: BMC Biochemistry - September 10, 2014 Category: Biochemistry Authors: Petra Van DammeKim PlasmanGiel VandemoorteleVeronique JonckheereSebastian Maurer-StrohKris Gevaert Source Type: research