The intracellular bacterium Orientia tsutsugamushi uses the autotransporter ScaC to activate BICD adaptors for dynein-based motility

IF 15.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Giulia Manigrasso, Kittirat Saharat, Panjaporn Chaichana, Chitrasak Kullapanich, Sharanjeet Atwal, Jerome Boulanger, Tomos E. Morgan, Holger Kramer, Jeanne Salje, Andrew P. Carter
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Abstract

The intracellular bacterium Orientia tsutsugamushi relies on the microtubule cytoskeleton and the motor protein dynein to traffic to the perinuclear region within infected cells. However, it remains unclear how the bacterium is coupled to the dynein machinery and how transport is regulated. Here, we discover that O. tsutsugamushi uses its autotransporter protein ScaC to recruit the dynein adaptors BICD1 and BICD2 for movement to the perinucleus. We show that ScaC is sufficient to engage dynein-based motility in the absence of other bacterial proteins and that BICD1 and BICD2 are required for efficient movement of O. tsutsugamushi during infection. Using TIRF single-molecule assays, we demonstrate that ScaC induces BICD2 to adopt an open conformation which activates the assembly of dynein-dynactin complexes. Our results reveal a role for BICD adaptors during bacterial infection and provide mechanistic insights into the life cycle of an important human pathogen.

Abstract Image

细胞内恙虫病东方菌使用自体转运体ScaC激活BICD适配器,以实现基于动力蛋白的运动
细胞内恙虫病东方杆菌依靠微管细胞骨架和运动蛋白动力蛋白运输到感染细胞内的核周区域。然而,目前尚不清楚细菌是如何与动力蛋白机制结合的,以及运输是如何被调节的。在这里,我们发现恙虫病体使用其自身转运蛋白ScaC招募动力蛋白适配器BICD1和BICD2运动到核周。我们发现ScaC在缺乏其他细菌蛋白的情况下足以参与基于动力蛋白的运动,BICD1和BICD2是恙虫病体感染期间有效运动所必需的。使用TIRF单分子分析,我们证明ScaC诱导BICD2采用开放构象,激活动力蛋白-动力蛋白复合物的组装。我们的研究结果揭示了BICD接头在细菌感染过程中的作用,并为一种重要人类病原体的生命周期提供了机制见解。
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来源期刊
Nature Communications
Nature Communications Biological Science Disciplines-
CiteScore
24.90
自引率
2.40%
发文量
6928
审稿时长
3.7 months
期刊介绍: Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.
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