9B85

Cryo-EM structure of human dynactin complex bound to Chlamydia effector Dre1

9B85 の概要

• エントリーDOI: 10.2210/pdb9b85/pdb
• EMDBエントリー: 44333
• 分子名称: Alpha-centractin, ADENOSINE-5'-DIPHOSPHATE, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (12 entities in total)
• 機能のキーワード: human dynactin, chlamydia effector, host-pathogen interaction, motor protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 19
• 化学式量合計: 767735.67

構造登録者

Pawar, K.I.,Verba, K.A. (登録日: 2024-03-28, 公開日: 2025-04-16)

主引用文献

Sherry, J.,Pawar, K.I.,Dolat, L.,Smith, E.,Chang, I.C.,Pha, K.,Kaake, R.,Swaney, D.L.,Herrera, C.,McMahon, E.,Bastidas, R.J.,Johnson, J.R.,Valdivia, R.H.,Krogan, N.J.,Elwell, C.A.,Verba, K.,Engel, J.N.
The Chlamydia effector Dre1 binds dynactin to reposition host organelles during infection.
Cell Rep, 44:115509-115509, 2025

PubMed Abstract: The obligate intracellular pathogen Chlamydia trachomatis replicates in a specialized membrane-bound compartment where it repositions host organelles during infection to acquire nutrients and evade host surveillance. We describe a bacterial effector, Dre1, that binds specifically to dynactin associated with host microtubule organizing centers without globally impeding dynactin function. Dre1 is required to reposition the centrosome, mitotic spindle, Golgi apparatus, and primary cilia around the inclusion and contributes to pathogen fitness in cell-based and mouse models of infection. We utilized Dre1 to affinity purify the megadalton dynactin protein complex and determined the first cryoelectron microscopy (cryo-EM) structure of human dynactin. Our results suggest that Dre1 binds to the pointed end of dynactin and uncovers the first bacterial effector that modulates dynactin function. Our work highlights how a pathogen employs a single effector to evoke targeted, large-scale changes in host cell organization that facilitate pathogen growth without inhibiting host viability.

PubMed: 40186871
DOI: 10.1016/j.celrep.2025.115509

実験手法

ELECTRON MICROSCOPY (3.47 Å)