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-Structure paper
タイトル | Structural insights into the activation mechanism of antimicrobial GBP1. |
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ジャーナル・号・ページ | EMBO J, Vol. 43, Issue 4, Page 615-636, Year 2024 |
掲載日 | 2024年1月24日 |
著者 | Marius Weismehl / Xiaofeng Chu / Miriam Kutsch / Paul Lauterjung / Christian Herrmann / Misha Kudryashev / Oliver Daumke / |
PubMed 要旨 | 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 ...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. |
リンク | EMBO J / PubMed:38267655 / PubMed Central |
手法 | EM (単粒子) / EM (サブトモグラム平均) |
解像度 | 26.8 - 37.0 Å |
構造データ | EMDB-18698: Structural insights into the activation mechanism of antimicrobial GBP1: Polymeric assembly of GBP1 EMDB-18806: Structural insights into the activation mechanism of antimicrobial GBP1: Membrane-bound GBP1 oligomer |
化合物 | ChemComp-AF3: ChemComp-MG: ChemComp-GDP: |
由来 |
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キーワード | ANTIMICROBIAL PROTEIN / Oligomer / GTPase / Interferon-induced |