MORC3 Is a Target of the Influenza A Viral Protein NS1

Yi Zhang, Jae Woo Ahn, Kelsie J. Green, Kendra R. Vann, Joshua Black, Christopher Byron Brooke, Tatiana G. Kutateladze

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1029-1033.e3
JournalStructure
Volume27
Issue number6
DOIs
StatePublished - Jun 4 2019

Fingerprint

Viral Proteins
Histones
Human Influenza
Adenosine Triphosphatases
Influenza A virus
Orthomyxoviridae
Tail
Catalytic Domain
Binding Sites
Ligands
Peptides
Proteins

Keywords

  • ATPase
  • CW
  • MORC3
  • NS1
  • chromatin
  • histone
  • immune
  • reader
  • structure
  • virus

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Zhang, Y., Ahn, J. W., Green, K. J., Vann, K. R., Black, J., Brooke, C. B., & Kutateladze, T. G. (2019). MORC3 Is a Target of the Influenza A Viral Protein NS1. Structure, 27(6), 1029-1033.e3. https://doi.org/10.1016/j.str.2019.03.015

MORC3 Is a Target of the Influenza A Viral Protein NS1. / Zhang, Yi; Ahn, Jae Woo; Green, Kelsie J.; Vann, Kendra R.; Black, Joshua; Brooke, Christopher Byron; Kutateladze, Tatiana G.

In: Structure, Vol. 27, No. 6, 04.06.2019, p. 1029-1033.e3.

Research output: Contribution to journalArticle

Zhang, Y, Ahn, JW, Green, KJ, Vann, KR, Black, J, Brooke, CB & Kutateladze, TG 2019, 'MORC3 Is a Target of the Influenza A Viral Protein NS1', Structure, vol. 27, no. 6, pp. 1029-1033.e3. https://doi.org/10.1016/j.str.2019.03.015
Zhang Y, Ahn JW, Green KJ, Vann KR, Black J, Brooke CB et al. MORC3 Is a Target of the Influenza A Viral Protein NS1. Structure. 2019 Jun 4;27(6):1029-1033.e3. https://doi.org/10.1016/j.str.2019.03.015
Zhang, Yi ; Ahn, Jae Woo ; Green, Kelsie J. ; Vann, Kendra R. ; Black, Joshua ; Brooke, Christopher Byron ; Kutateladze, Tatiana G. / MORC3 Is a Target of the Influenza A Viral Protein NS1. In: Structure. 2019 ; Vol. 27, No. 6. pp. 1029-1033.e3.
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