Dataset Information

Identification of RON13 binding with with RON4 substrate

ABSTRACT: Active host cell invasion by the obligate intracellular apicomplexan parasites relies on the formation of a moving junction (MJ), which joins parasite and host cell plasma membranes during entry. Invading Toxoplasma gondii tachyzoites secrete a complex of RON proteins from the rhoptry organelles that provide the components of the MJ on the cytoplasmic side of the host cell membrane. This study highlights the role of a rhoptry resident kinase, RON13, that plays a crucial role during host cell entry and is a virulence factor in the mouse model of infection. Comparative phosphoproteomics demonstrated RON13-dependent phosphorylation of secreted rhoptry proteins and primarily the RONs complex. Structural and biochemical analysis of RON13 revealed the atypical nature of this active secretory pathway kinase, unique to the Apicomplexa.

INSTRUMENT(S): LTQ Velos

ORGANISM(S): Toxoplasma Gondii Gt1

SUBMITTER: Oscar Vadas

LAB HEAD: Dominique Soldati-Favre

PROVIDER: PXD023791 | Pride | 2021-05-10

REPOSITORIES: Pride

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Publications

Structural insights into an atypical secretory pathway kinase crucial for Toxoplasma gondii invasion.

Lentini Gaëlle G Ben Chaabene Rouaa R Vadas Oscar O Ramakrishnan Chandra C Mukherjee Budhaditya B Mehta Ved V Lunghi Matteo M Grossmann Jonas J Maco Bohumil B Visentin Rémy R Hehl Adrian B AB Korkhov Volodymyr M VM Soldati-Favre Dominique D

Nature communications 20210618 1

Active host cell invasion by the obligate intracellular apicomplexan parasites relies on the formation of a moving junction, which connects parasite and host cell plasma membranes during entry. Invading Toxoplasma gondii tachyzoites secrete their rhoptry content and insert a complex of RON proteins on the cytoplasmic side of the host cell membrane providing an anchor to which the parasite tethers. Here we show that a rhoptry-resident kinase RON13 is a key virulence factor that plays a crucial ro ...[more]

PMID: 34145271

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Project description:Multiple respiratory viruses including Influenza A virus (IAV) can be transmitted via expiratory aerosol particles, and many studies have established that environmental conditions can affect viral infectivity during airborne transmission. Low aerosol pH was recently identified as a major factor influencing the infectivity of aerosol-borne IAV and SARS-CoV-2, however, there is a fundamental lack of understanding as to the mechanisms leading to viral inactivation within the acidic aerosol micro-environment. Here, we identified that the early stages of the IAV infection cycle were impacted by transient exposure to acidic aerosol conditions (pH below 5.5), which was primarily attributed to loss of binding function of the viral protein haemagglutinin. Viral capsid integrity was also somewhat affected by transient acidic exposure. We then characterised the structural changes associated with loss of viral infectivity using whole-virus hydrogen-deuterium exchange coupled to mass spectrometry (HDX-MS), and observed discrete regions of unfolding in the external viral protein haemagglutinin and in the internal matrix protein 1. Viral nucleoprotein structure appeared to be unaffected by exposure to acidic aerosol conditions, and no changes to viral genome integrity or to lipids within the viral envelope were detected using our whole-virus methods. Collectively, these data indicate that viral inactivation observed under indoor aerosol conditions is mediated by specific protein conformational changes, particularly to haemagglutinin. This study additionally provides a proof-of-concept that HDX-MS is a highly effective method for characterisation of internal and external proteins of whole enveloped viruses such as IAV. Overall, improved understanding of the fate of respiratory viruses within exhaled aerosols will aid the development of novel strategies and therapeutics to control the severity of seasonal and/or pandemic influenza, and constitutes a global public health priority.

Dataset Information

Identification of RON13 binding with with RON4 substrate

Publications

Structural insights into an atypical secretory pathway kinase crucial for Toxoplasma gondii invasion.

Similar Datasets

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