5WRV

Complex structure of human SRP72/SRP68

5WRV の概要

• エントリーDOI: 10.2210/pdb5wrv/pdb
• 関連するPDBエントリー: 5WRW
• 分子名称: Signal recognition particle subunit SRP68, Signal recognition particle subunit SRP72, ACETATE ION, ... (7 entities in total)
• 機能のキーワード: complex, human, srp72, srp68, signal recognition particle, protein transport
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cytoplasm: Q9UHB9 O76094
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 30899.57

構造登録者

Gao, Y.,Chen, Z. (登録日: 2016-12-04, 公開日: 2017-06-21, 最終更新日: 2024-03-20)

主引用文献

Gao, Y.,Zhang, Q.,Lang, Y.,Liu, Y.,Dong, X.,Chen, Z.,Tian, W.,Tang, J.,Wu, W.,Tong, Y.,Chen, Z.
Human apo-SRP72 and SRP68/72 complex structures reveal the molecular basis of protein translocation
J Mol Cell Biol, 9:220-230, 2017

PubMed Abstract: The co-translational targeting or insertion of secretory and membrane proteins into the endoplasmic reticulum (ER) is a key biological process mediated by the signal recognition particle (SRP). In eukaryotes, the SRP68-SRP72 (SRP68/72) heterodimer plays an essential role in protein translocation. However, structural information on the two largest SRP proteins, SRP68 and SRP72, is limited, especially regarding their interaction. Herein, we report the first crystal structures of human apo-SRP72 and the SRP68/72 complex at 2.91Å and 1.7Å resolution, respectively. The SRP68-binding domain of SRP72 contains four atypical tetratricopeptide repeats (TPR) and a flexible C-terminal cap. Apo-SRP72 exists mainly as dimers in solution. To bind to SRP68, the SRP72 homodimer disassociates, and the indispensable C-terminal cap undergoes a pronounced conformational change to assist formation of the SRP68/72 heterodimer. A 23-residue polypeptide of SRP68 is sufficient for tight binding to SRP72 through its unusually hydrophobic and extended surface. Structural, biophysical, and mutagenesis analyses revealed that cancer-associated mutations disrupt the SRP68-SRP72 interaction and their co-localization with ER in mammalian cells. The results highlight the essential role of the SRP68-SRP72 interaction in SRP-mediated protein translocation and provide a structural basis for disease diagnosis, pathophysiology, and drug design.

PubMed: 28369529
DOI: 10.1093/jmcb/mjx010

実験手法

X-RAY DIFFRACTION (1.7 Å)