DOI: 10.1101/494930Dec 13, 2018Paper

Kinetic And Structural Parameters Governing Fic-Mediated Adenylylation/AMPylation of the Hsp70 chaperone, BiP/GRP78

BioRxiv : the Preprint Server for Biology
Seema MattooDaisuke Kihara


Fic (filamentation induced by cAMP) proteins regulate diverse cell signaling events by post-translationally modifying their protein targets, predominantly by the addition of an AMP (adenosine monophosphate). This modification is called Fic-mediated Adenylylation or AMPylation. We previously reported that the human Fic protein, HYPE/FicD, is a novel regulator of the unfolded protein response (UPR) that maintains homeostasis in the endoplasmic reticulum (ER) in response to stress from misfolded proteins. Specifically, HYPE regulates UPR by adenylylating the ER chaperone, BiP/GRP78, which serves as a sentinel for UPR activation. Maintaining ER homeostasis is critical for determining cell fate, thus highlighting the importance of the HYPE-BiP interaction. Here, we study the kinetic and structural parameters that determine the HYPE-BiP interaction. By measuring the binding and kinetic efficiencies of HYPE in its activated (Adenylylation-competent) and wild type (de-AMPylation-competent) forms for BiP in its wild type and ATP-bound conformations, we determine that HYPE displays a nearly identical preference for the wild type and ATP-bound forms of BiP in vitro and preferentially de-AMPylates the wild type form of adenylylated BiP. We...Continue Reading

Related Concepts

Adenosine Triphosphate
Endoplasmic Reticulum
adenosine monophosphate-adenosine
Molecular Chaperones
Recognition (Psychology)

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