8R1A

Model of the membrane-bound GBP1 oligomer

8R1A の概要

• エントリーDOI: 10.2210/pdb8r1a/pdb
• EMDBエントリー: 18806
• 分子名称: Guanylate binding protein 1, ALUMINUM FLUORIDE, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: oligomer, gtpase, interferon-induced, antimicrobial protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 418916.48

構造登録者

Weismehl, M.,Chu, X.,Kutsch, M.,Lauterjung, P.,Herrmann, C.,Kudryashev, M.,Daumke, O. (登録日: 2023-11-01, 公開日: 2024-01-17, 最終更新日: 2024-02-28)

主引用文献

Weismehl, M.,Chu, X.,Kutsch, M.,Lauterjung, P.,Herrmann, C.,Kudryashev, M.,Daumke, O.
Structural insights into the activation mechanism of antimicrobial GBP1.
Embo J., 43:615-636, 2024

PubMed Abstract: The dynamin-related human guanylate-binding protein 1 (GBP1) mediates host defenses against microbial pathogens. Upon GTP binding and hydrolysis, auto-inhibited GBP1 monomers dimerize and assemble into soluble and membrane-bound oligomers, which are crucial for innate immune responses. How higher-order GBP1 oligomers are built from dimers, and how assembly is coordinated with nucleotide-dependent conformational changes, has remained elusive. Here, we present cryo-electron microscopy-based structural data of soluble and membrane-bound GBP1 oligomers, which show that GBP1 assembles in an outstretched dimeric conformation. We identify a surface-exposed helix in the large GTPase domain that contributes to the oligomerization interface, and we probe its nucleotide- and dimerization-dependent movements that facilitate the formation of an antimicrobial protein coat on a gram-negative bacterial pathogen. Our results reveal a sophisticated activation mechanism for GBP1, in which nucleotide-dependent structural changes coordinate dimerization, oligomerization, and membrane binding to allow encapsulation of pathogens within an antimicrobial protein coat.

PubMed: 38267655
DOI: 10.1038/s44318-023-00023-y

実験手法

ELECTRON MICROSCOPY (26.8 Å)