Structural basis for histone mimicry and hijacking of host proteins by influenza virus protein NS1

Su Qin; Yanli Liu; Wolfram Tempel; Mohammad S Eram; Chuanbing Bian; Ke Liu; Guillermo Senisterra; Lissete Crombet; Masoud Vedadi; Jinrong Min

doi:10.1038/ncomms4952

Structural basis for histone mimicry and hijacking of host proteins by influenza virus protein NS1

Nat Commun. 2014 May 23:5:3952. doi: 10.1038/ncomms4952.

Authors

Affiliations

¹ 1] Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Science, Central China Normal University, Wuhan 430079, PR China [2] Structural Genomics Consortium, University of Toronto, 101 College Street, Toronto, Ontario, Canada M5G 1L7 [3].
² Structural Genomics Consortium, University of Toronto, 101 College Street, Toronto, Ontario, Canada M5G 1L7.
³ 1] Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Science, Central China Normal University, Wuhan 430079, PR China [2] Structural Genomics Consortium, University of Toronto, 101 College Street, Toronto, Ontario, Canada M5G 1L7.
⁴ 1] Structural Genomics Consortium, University of Toronto, 101 College Street, Toronto, Ontario, Canada M5G 1L7 [2] Department of Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8.
⁵ 1] Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Science, Central China Normal University, Wuhan 430079, PR China [2] Structural Genomics Consortium, University of Toronto, 101 College Street, Toronto, Ontario, Canada M5G 1L7 [3] Department of Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8.

PMID: 24853335
DOI: 10.1038/ncomms4952

Abstract

Pathogens can interfere with vital biological processes of their host by mimicking host proteins. The NS1 protein of the influenza A H3N2 subtype possesses a histone H3K4-like sequence at its carboxyl terminus and has been reported to use this mimic to hijack host proteins. However, this mimic lacks a free N-terminus that is essential for binding to many known H3K4 readers. Here we show that the double chromodomains of CHD1 adopt an 'open pocket' to interact with the free N-terminal amine of H3K4, and the open pocket permits the NS1 mimic to bind in a distinct conformation. We also explored the possibility that NS1 hijacks other cellular proteins and found that the NS1 mimic has access to only a subset of chromatin-associated factors, such as WDR5. Moreover, methylation of the NS1 mimic can not be reversed by the H3K4 demethylase LSD1. Overall, we thus conclude that the NS1 mimic is an imperfect histone mimic.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Amino Acid Motifs
Amino Acid Sequence
Calorimetry
Crystallography, X-Ray
DNA Helicases / metabolism
DNA-Binding Proteins / metabolism
Histone Demethylases / metabolism
Histone-Lysine N-Methyltransferase / metabolism
Histones / metabolism*
Host-Pathogen Interactions*
Humans
Influenza A Virus, H3N2 Subtype / metabolism
Intracellular Signaling Peptides and Proteins
Mass Spectrometry
Methylation
Models, Molecular
Molecular Sequence Data
Peptides / metabolism
Protein Binding
Protein Structure, Tertiary
Sequence Alignment
Structure-Activity Relationship
Viral Nonstructural Proteins / chemistry*
Viral Nonstructural Proteins / metabolism*

Substances

DNA-Binding Proteins
Histones
INS1 protein, influenza virus
Intracellular Signaling Peptides and Proteins
Peptides
Viral Nonstructural Proteins
WDR5 protein, human
Histone Demethylases
KDM1A protein, human
Histone-Lysine N-Methyltransferase
DNA Helicases
CHD1 protein, human

Associated data

PDB/4NW2
PDB/4O42
PDB/4O45
PDB/WDR5

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding