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Sökning: onr:"swepub:oai:DiVA.org:umu-182922" > Specificity of AMPy...

Specificity of AMPylation of the human chaperone BiP is mediated by TPR motifs of FICD

Fauser, Joel (författare)
Department of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany; Center for Integrated Protein Science Munich (CIPSM), Department Chemistry, Technical University of Munich, Garching, Germany
Gulen, Burak (författare)
Department of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany; Center for Integrated Protein Science Munich (CIPSM), Department Chemistry, Technical University of Munich, Garching, Germany
Pogenberg, Vivian (författare)
Department of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany
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Pett, Christian (författare)
Umeå universitet,Kemiska institutionen
Pourjafar-Dehkordi, Danial (författare)
Physics Department T38, Technical University of Munich, Garching, Germany
Krisp, Christoph (författare)
Institute of Clinical Chemistry and Laboratory Medicine, Mass Spectrometric Proteomics, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany
Höpfner, Dorothea (författare)
Department of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany; Center for Integrated Protein Science Munich (CIPSM), Department Chemistry, Technical University of Munich, Garching, Germany
König, Gesa (författare)
Department of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany
Schlüter, Hartmut (författare)
Institute of Clinical Chemistry and Laboratory Medicine, Mass Spectrometric Proteomics, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany
Feige, Matthias J. (författare)
Center for Integrated Protein Science Munich (CIPSM), Department Chemistry, Technical University of Munich, Garching, Germany; Institute for Advanced Study, Technical University of Munich, Garching, Germany
Zacharias, Martin (författare)
Physics Department T38, Technical University of Munich, Garching, Germany
Hedberg, Christian (författare)
Umeå universitet,Kemiska institutionen
Itzen, Aymelt (författare)
Department of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany; Center for Integrated Protein Science Munich (CIPSM), Department Chemistry, Technical University of Munich, Garching, Germany; Center for Structural Systems Biology (CSSB), University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany
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 (creator_code:org_t)
2021-04-23
2021
Engelska.
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • To adapt to fluctuating protein folding loads in the endoplasmic reticulum (ER), the Hsp70 chaperone BiP is reversibly modified with adenosine monophosphate (AMP) by the ER-resident Fic-enzyme FICD/HYPE. The structural basis for BiP binding and AMPylation by FICD has remained elusive due to the transient nature of the enzyme-substrate-complex. Here, we use thiol-reactive derivatives of the cosubstrate adenosine triphosphate (ATP) to covalently stabilize the transient FICD:BiP complex and determine its crystal structure. The complex reveals that the TPR-motifs of FICD bind specifically to the conserved hydrophobic linker of BiP and thus mediate specificity for the domain-docked conformation of BiP. Furthermore, we show that both AMPylation and deAMPylation of BiP are not directly regulated by the presence of unfolded proteins. Together, combining chemical biology, crystallography and biochemistry, our study provides structural insights into a key regulatory mechanism that safeguards ER homeostasis.

Ämnesord

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
NATURVETENSKAP  -- Biologi -- Strukturbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Structural Biology (hsv//eng)

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