Virtually all aspects of cell biology are regulated by a ubiquitin code where distinct ubiquitin chain architectures guide the binding events and itineraries of modified substrates. Various combinations of E2 and E3 enzymes accomplish chain formation by forging isopeptide bonds between the C terminus of their transiently linked donor ubiquitin and a specific nucleophilic amino acid on the acceptor ubiquitin, yet it is unknown whether the fundamental feature of most acceptors—the lysine side chain—affects catalysis. Here, use of synthetic ubiquitins with non-natural acceptor site replacements reveals that the aliphatic side chain specifying reactive amine geometry is a determinant of the ubiquitin code, through unanticipated and complex reliance of many distinct ubiquitin-carrying enzymes on a canonical acceptor lysine.

几乎细胞生物学的所有方面都由泛素代码调节，其中不同的泛素链结构指导修饰底物的结合事件和路线。E2和E3酶的各种组合通过在其瞬时连接的供体泛素的C末端与受体泛素上的特定亲核氨基酸之间形成异肽键来完成链形成，但尚不清楚大多数受体的基本特征是否是赖氨酸侧链——影响催化。在这里，使用具有非天然受体位点替换的合成泛素表明，通过许多不同的泛素携带酶对规范受体赖氨酸的出乎意料和复杂的依赖，指定反应性胺几何形状的脂肪族侧链是泛素代码的决定因素。