MORC3 Is a Target of the Influenza A Viral Protein NS1

Yi Zhang; JaeWoo Ahn; Kelsie J Green; Kendra R Vann; Joshua Black; Christopher B Brooke; Tatiana G Kutateladze

doi:10.1016/j.str.2019.03.015

MORC3 Is a Target of the Influenza A Viral Protein NS1

Structure. 2019 Jun 4;27(6):1029-1033.e3. doi: 10.1016/j.str.2019.03.015. Epub 2019 Apr 18.

Authors

Yi Zhang¹, JaeWoo Ahn¹, Kelsie J Green², Kendra R Vann¹, Joshua Black¹, Christopher B Brooke³, Tatiana G Kutateladze⁴

Affiliations

¹ Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
² Department of Microbiology, University of Illinois, Urbana, IL 61801, USA.
³ Department of Microbiology, University of Illinois, Urbana, IL 61801, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois, Urbana, IL 61801, USA.
⁴ Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA. Electronic address: tatiana.kutateladze@ucdenver.edu.

PMID: 31006586
DOI: 10.1016/j.str.2019.03.015

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.

Keywords: ATPase; CW; MORC3; NS1; chromatin; histone; immune; reader; structure; virus.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Triphosphatases / chemistry*
Adenosine Triphosphatases / metabolism
Binding, Competitive
Crystallography, X-Ray
DNA-Binding Proteins / chemistry*
DNA-Binding Proteins / metabolism
Histones / chemistry
Histones / metabolism
Humans
Influenza A Virus, H3N2 Subtype / metabolism*
Influenza A Virus, H3N2 Subtype / physiology
Influenza, Human / metabolism*
Influenza, Human / virology
Models, Molecular
Protein Binding
Protein Domains*
Viral Nonstructural Proteins / chemistry*
Viral Nonstructural Proteins / genetics
Viral Nonstructural Proteins / metabolism

Substances

DNA-Binding Proteins
Histones
INS1 protein, influenza virus
Viral Nonstructural Proteins
Adenosine Triphosphatases
MORC3 protein, human