김배훈 (Yale University, 현 PRG S&Tech(피알지에스앤텍))

한빛사논문

조회469

Yale University, 현 PRG S&Tech(피알지에스앤텍)

CV File 376 kb

Science, Mar 2024, 383 (6686) | https://doi.org/10.1126/science.abm9903 Native architecture of a human GBP1 defense complex for cell-autonomous immunity to infection

Shiwei Zhu ^{# 1 2 3 4}, Clinton J Bradfield ^{# 1 2 3 4}, Agnieszka Maminska ^{# 1 2 3 4}, Eui-Soon Park ^{# 1 2 3 4}, Bae-Hoon Kim ^{# 1 2 3 4}, Pradeep Kumar ^{1 2 3 4}, Shuai Huang ^{1 2 3 4}, Minjeong Kim^{1 2 3 4}, Yongdeng Zhang ⁵, Joerg Bewersdorf^{5 6}, John D MacMicking ^{1 2 3 4 *}

¹Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.

²Yale Systems Biology Institute, West Haven, CT 06477, USA.

³Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510, USA.

⁴Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.

⁵Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510, USA.

⁶Yale Nanobiology Institute, West Haven, CT 06477, USA.

^#Contributed equally.
^*Corresponding author: correspondence to John D MacMicking

Abstract

All living organisms deploy cell-autonomous defenses to combat infection. In plants and animals, large supramolecular complexes often activate immune proteins for protection. In this work, we resolved the native structure of a massive host-defense complex that polymerizes 30,000 guanylate-binding proteins (GBPs) over the surface of gram-negative bacteria inside human cells. Construction of this giant nanomachine took several minutes and remained stable for hours, required guanosine triphosphate hydrolysis, and recruited four GBPs plus caspase-4 and Gasdermin D as a cytokine and cell death immune signaling platform. Cryo-electron tomography suggests that GBP1 can adopt an extended conformation for bacterial membrane insertion to establish this platform, triggering lipopolysaccharide release that activated coassembled caspase-4. Our "open conformer" model provides a dynamic view into how the human GBP1 defense complex mobilizes innate immunity to infection.

논문정보

형식Research article
게재일2024년 03월 (BRIC 등록일 2024-03-05)
연구진국외 연구진
분야 생명과학 > 감염생물학

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