Dissection of influenza A virus M1 protein: pH-dependent oligomerization of N-terminal domain and dimerization of C-terminal domain.
BACKGROUND
The matrix 1 (M1) protein of Influenza A virus plays many critical roles throughout the virus life cycle. The oligomerization of M1 is essential for the formation of the viral matrix layer during the assembly and budding process.


RESULTS
In the present study, we report that M1 can oligomerize in vitro, and that the oligomerization is pH-dependent. The N-terminal domain of M1 alone exists as multiple-order oligomers at pH 7.4, and the C-terminal domain alone forms an exclusively stable dimer. As a result, intact M1 can display different forms of oligomers and dimer is the smallest oligomerization state, at neutral pH. At pH 5.0, oligomers of the N-terminal domain completely dissociate into monomers, while the C-terminal domain remains in dimeric form. As a result, oligomers of intact M1 dissociate into a stable dimer at acidic pH.


CONCLUSIONS
Oligomerization of M1 involves both the N- and C-terminal domains. The N-terminal domain determines the pH-dependent oligomerization characteristic, and C-terminal domain forms a stable dimer, which contributes to the dimerization of M1. The present study will help to unveil the mechanisms of influenza A virus assembly and uncoating process.
Center for Molecular Virology, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Ke
K
Zhang
Zhao
Z
Wang
Xiaoling
X
Liu
Changcheng
C
Yin
Zeshan
Z
Basit
Bin
B
Xia
Wenjun
W
Liu
D000818:Animals; D002645:Chickens / Q000821:virology*; D006863:Hydrogen-Ion Concentration; D053127:Influenza A Virus, H9N2 Subtype / Q000737:chemistry*; D009980:Influenza A virus / Q000737:chemistry*; D005585:Influenza in Birds / Q000821:virology*; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary