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

Standard

Specificity of AMPylation of the human chaperone BiP is mediated by TPR motifs of FICD. / Fauser, Joel; Gulen, Burak; Pogenberg, Vivian; Pett, Christian; Pourjafar-Dehkordi, Danial; Krisp, Christoph; Höpfner, Dorothea; König, Gesa; Schlüter, Hartmut; Feige, Matthias J; Zacharias, Martin; Hedberg, Christian; Itzen, Aymelt.

in: NAT COMMUN, Jahrgang 12, Nr. 1, 2426, 23.04.2021.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Fauser, J, Gulen, B, Pogenberg, V, Pett, C, Pourjafar-Dehkordi, D, Krisp, C, Höpfner, D, König, G, Schlüter, H, Feige, MJ, Zacharias, M, Hedberg, C & Itzen, A 2021, 'Specificity of AMPylation of the human chaperone BiP is mediated by TPR motifs of FICD', NAT COMMUN, Jg. 12, Nr. 1, 2426. https://doi.org/10.1038/s41467-021-22596-0

APA

Fauser, J., Gulen, B., Pogenberg, V., Pett, C., Pourjafar-Dehkordi, D., Krisp, C., Höpfner, D., König, G., Schlüter, H., Feige, M. J., Zacharias, M., Hedberg, C., & Itzen, A. (2021). Specificity of AMPylation of the human chaperone BiP is mediated by TPR motifs of FICD. NAT COMMUN, 12(1), [2426]. https://doi.org/10.1038/s41467-021-22596-0

Vancouver

Fauser J, Gulen B, Pogenberg V, Pett C, Pourjafar-Dehkordi D, Krisp C et al. Specificity of AMPylation of the human chaperone BiP is mediated by TPR motifs of FICD. NAT COMMUN. 2021 Apr 23;12(1). 2426. https://doi.org/10.1038/s41467-021-22596-0

Bibtex

@article{672c98f136b94a8db2d149c344e79dc1,
title = "Specificity of AMPylation of the human chaperone BiP is mediated by TPR motifs of FICD",
abstract = "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.",
author = "Joel Fauser and Burak Gulen and Vivian Pogenberg and Christian Pett and Danial Pourjafar-Dehkordi and Christoph Krisp and Dorothea H{\"o}pfner and Gesa K{\"o}nig and Hartmut Schl{\"u}ter and Feige, {Matthias J} and Martin Zacharias and Christian Hedberg and Aymelt Itzen",
year = "2021",
month = apr,
day = "23",
doi = "10.1038/s41467-021-22596-0",
language = "English",
volume = "12",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - Specificity of AMPylation of the human chaperone BiP is mediated by TPR motifs of FICD

AU - Fauser, Joel

AU - Gulen, Burak

AU - Pogenberg, Vivian

AU - Pett, Christian

AU - Pourjafar-Dehkordi, Danial

AU - Krisp, Christoph

AU - Höpfner, Dorothea

AU - König, Gesa

AU - Schlüter, Hartmut

AU - Feige, Matthias J

AU - Zacharias, Martin

AU - Hedberg, Christian

AU - Itzen, Aymelt

PY - 2021/4/23

Y1 - 2021/4/23

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-021-22596-0

DO - 10.1038/s41467-021-22596-0

M3 - SCORING: Journal article

C2 - 33893288

VL - 12

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

IS - 1

M1 - 2426

ER -