MORC3 Is a Target of the Influenza A Viral Protein NS1

Overview

Journal Structure

Publisher Cell Press

Specialties Biochemistry
Biotechnology
Cell Biology
Molecular Biology

Date 2019 Apr 23

PMID 31006586

Citations 10

Authors

Yi Zhang

JaeWoo Ahn

Kelsie J Green

Kendra R Vann

Joshua Black

Christopher B Brooke

Tatiana G Kutateladze

Affiliations

Soon will be listed here.

Abstract

Microrchidia 3 (MORC3), a human ATPase linked to several autoimmune disorders, has been characterized both as a negative and positive regulator of influenza A virus. Here, we report that the CW domain of MORC3 (MORC3-CW) is targeted by the C-terminal tail of the influenza H3N2 protein NS1. The crystal structure of the MORC3-CW:NS1 complex shows that NS1 occupies the same binding site in CW that is normally occupied by histone H3, a physiological ligand of MORC3-CW. Comparable binding affinities of MORC3-CW to H3 and NS1 peptides and to the adjacent catalytic ATPase domain suggest that the viral protein can compete with the host histone for the association with CW, releasing MORC3 autoinhibition and activating the catalytic function of MORC3. Our structural, biochemical, and cellular analyses suggest that MORC3 might affect the infectivity of influenza virus and therefore has a role in cell immune response.

Citing Articles

Structural Investigations of Interactions between the Influenza a Virus NS1 and Host Cellular Proteins.

Blake M, Kleinpeter A, Jureka A, Petit C Viruses. 2023; 15(10).

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Antiviral effects of interferon-stimulated genes in bats.

Zhang D, Irving A Front Cell Infect Microbiol. 2023; 13:1224532.

PMID: 37661999 PMC: 10472940. DOI: 10.3389/fcimb.2023.1224532.

Vital for Viruses: Intrinsically Disordered Proteins.

Dyson H J Mol Biol. 2023; 435(11):167860.

PMID: 37330280 PMC: 10656058. DOI: 10.1016/j.jmb.2022.167860.

Non-histone binding functions of PHD fingers.

Gaurav N, Kutateladze T Trends Biochem Sci. 2023; 48(7):610-617.

PMID: 37061424 PMC: 10330121. DOI: 10.1016/j.tibs.2023.03.005.

Self-guarding of MORC3 enables virulence factor-triggered immunity.

Gaidt M, Morrow A, Fairgrieve M, Karr J, Yosef N, Vance R Nature. 2021; 600(7887):138-142.

PMID: 34759314 PMC: 9045311. DOI: 10.1038/s41586-021-04054-5.

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