DPP8/9 processing of human AK2 unmasks an IAP binding motif

AK2 is n-terminally processed by methionine aminopeptidases, N-terminal acetylation and DDP8/9 to become an active protein which is then sorted in the mitochondrial intermembrane space. We used peptide pull-downs of free and acetylated N-terminal peptides of AK2 from the different processing steps to identify binding partners by MS. We identified the inhibitor of apoptosis E3 ligase proteins (IAPs; BIRC2, 3, 6 and XIAP) as new binding partners for processed AK2 and show that they are responsible for AK2 degradation in the cytosol.AK2经甲硫氨酸氨肽酶、N端乙酰化修饰及DDP8/9完成N端加工，成为活性蛋白后被分选至线粒体膜间隙。我们针对不同加工阶段的AK2游离型与乙酰化型N端肽段开展肽下拉实验，通过质谱（Mass Spectrometry，MS）鉴定其结合伴侣。本研究鉴定得到凋亡抑制E3泛素连接酶蛋白（Inhibitor of Apoptosis Proteins，IAPs；包含BIRC2、3、6及XIAP）为加工后AK2的新型结合伴侣，并证实它们介导了AK2在细胞质中的降解。