Moonlighting Peptides with Emerging Function

Hunter-killer peptides combine two activities in a single polypeptide that work in an independent fashion like many other multi-functional, multi-domain proteins. We hypothesize that emergent functions may result from the combination of two or more activities in a single protein domain and that could be a mechanism selected in nature to form moonlighting proteins. We designed moonlighting peptides using the two mechanisms proposed to be involved in the evolution of such molecules (i.e., to mutate non-functional residues and the use of natively unfolded peptides). We observed that our moonlighting peptides exhibited two activities that together rendered a new function that induces cell death in yeast. Thus, we propose that moonlighting in proteins promotes emergent properties providing a further level of complexity in living organisms so far unappreciated.杀伤肽（Hunter-killer peptides）是一类可在单条多肽链中同时兼具两种独立活性的分子，其功能模式与诸多其他多功能多结构域蛋白质相仿。我们提出假说：单个蛋白质结构域内两种或多种活性的组合可催生涌现功能，而这或许是自然界中用于形成兼职蛋白（moonlighting proteins）的一种被选择的演化机制。我们采用两类已被提出、参与这类分子演化的机制设计了兼职肽：一是对非功能性残基进行诱变，二是利用天然未折叠肽（natively unfolded peptides）。实验观察显示，我们设计的兼职肽具备两种活性，二者协同作用可产生一种全新功能，能够诱导酵母细胞死亡。据此我们提出，蛋白质的兼职现象可催生涌现属性，为生命体增添了此前尚未被认知的又一重复杂性。