Structural basis of chaperone regulation by a post-translational modification

The Hsp70 chaperone BiP is covalently modified with adenosine monophosphate (referred to as AMPylation) in order to adapt its activity to the fluctuating folding load within the endoplasmic reticulum. This modification is catalyzed by the only human representative of the family of filamentation induced by cyclic adenosine monophosphate (Fic) enzymes HYPE/FICD. The structural basis for BiP binding and AMPylation has remained elusive due to the low affinity of enzyme substrate complexes.

热休克蛋白70（Hsp70）伴侣蛋白BiP可通过共价结合一磷酸腺苷（adenosine monophosphate, AMP）发生修饰，该修饰过程被称为一磷酸腺苷酰化（AMPylation），以此调节其活性以适应内质网（endoplasmic reticulum）内动态变化的蛋白质折叠负荷。该修饰反应由环腺苷单磷酸诱导丝状化（filamentation induced by cyclic adenosine monophosphate, Fic）酶家族在人体内的唯一成员HYPE/FICD催化。由于酶-底物复合物的亲和力较低，BiP结合与AMPylation的结构基础至今仍未明确。