6ZMD

Crystal structure of HYPE covalently tethered to BiP bound to AMP-PNP

6ZMD の概要

• エントリーDOI: 10.2210/pdb6zmd/pdb
• 分子名称: Endoplasmic reticulum chaperone BiP, Protein adenylyltransferase FICD, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (7 entities in total)
• 機能のキーワード: ampylation, endoplasmic reticulum, fic enzyme, chaperone, post-translational modification, transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 98330.51

構造登録者

Fauser, J.,Gulen, B.,Pett, C.,Hedberg, C.,Itzen, A.,Pogenberg, V. (登録日: 2020-07-02, 公開日: 2021-04-14, 最終更新日: 2024-10-16)

主引用文献

Fauser, J.,Gulen, B.,Pogenberg, V.,Pett, C.,Pourjafar-Dehkordi, D.,Krisp, C.,Hopfner, D.,Konig, G.,Schluter, H.,Feige, M.J.,Zacharias, M.,Hedberg, C.,Itzen, A.
Specificity of AMPylation of the human chaperone BiP is mediated by TPR motifs of FICD.
Nat Commun, 12:2426-2426, 2021

PubMed 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.

PubMed: 33893288
DOI: 10.1038/s41467-021-22596-0

実験手法

X-RAY DIFFRACTION (2.64 Å)