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Specificity of AMPy...
Specificity of AMPylation of the human chaperone BiP is mediated by TPR motifs of FICD
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- Fauser, Joel (author)
- 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
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- Gulen, Burak (author)
- 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
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- Pogenberg, Vivian (author)
- Department of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany
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- Pett, Christian (author)
- Umeå universitet,Kemiska institutionen
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- Pourjafar-Dehkordi, Danial (author)
- Physics Department T38, Technical University of Munich, Garching, Germany
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- Krisp, Christoph (author)
- Institute of Clinical Chemistry and Laboratory Medicine, Mass Spectrometric Proteomics, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany
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- Höpfner, Dorothea (author)
- 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
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- König, Gesa (author)
- Department of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany
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- Schlüter, Hartmut (author)
- Institute of Clinical Chemistry and Laboratory Medicine, Mass Spectrometric Proteomics, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany
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- Feige, Matthias J. (author)
- 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
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- Zacharias, Martin (author)
- Physics Department T38, Technical University of Munich, Garching, Germany
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- Hedberg, Christian (author)
- Umeå universitet,Kemiska institutionen
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- Itzen, Aymelt (author)
- 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
- English.
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
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Abstract
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- 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.
Subject headings
- 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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- ref (subject category)
- art (subject category)
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- By the author/editor
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Fauser, Joel
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Gulen, Burak
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Pogenberg, Vivia ...
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Pett, Christian
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Pourjafar-Dehkor ...
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Krisp, Christoph
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Höpfner, Dorothe ...
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König, Gesa
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Schlüter, Hartmu ...
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Feige, Matthias ...
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Zacharias, Marti ...
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Hedberg, Christi ...
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Itzen, Aymelt
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Structural Biolo ...
- Articles in the publication
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Nature Communica ...
- By the university
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Umeå University