ИСТИНА

Influenza A viruses still remains one of the most serious global health problems. One of the most important and abundant proteins of the virus is matrix protein M1. It plays essential structural and functional roles in the virus life cycle [1]. The absence of high-resolution data on the full-length M1 makes the structural analysis of the intact protein very important, but especially crucial is to study the structure of the protein in solution, i.e. at conditions most close to physiological. However, it is well known that the isolated M1 can be soluble only at pH < 5.0 [2]. This condition occurs at the very beginning of cell infection leading to an acid-triggered fusion of the viral membrane. Moreover, change of pH was found to serve as a switch that allows M1 to carry out its multiple functions [3]. It was recently demonstrated that M1 forms large associates even at acidic pH [4]. Hence, the association tendency of M1 should increase with pH. Our analysis of the structure and self-assembly of M1 at gradually changing pH in solution (by SAXS) and on the bare mica surface (by AFM) demonstrated formation of well ordered helix-like shapes. We found that the association processes occur in a similar way in the solution and on the substrate, and quantitatively described these processes. Moreover, pH 6.0 was found to be the condition at which binding between M1 molecules starts to break. The observed helix-like formations could be treated as pre-matrix protein superstructures or virus-like particles, whose formation is an intrinsic biological property of the M1 protein. These results provide new insights into the mechanism of M1 to form matrix or virus-like particles alone without partners and give a basis for a further analysis of the hierarchy of M1 in the virus life cycle This work was supported in part by Russian Foundation for Basic Researches (projects 15-54-74002 EMBL_а and 16-04-00563). References: 1. D. Nayak et al. Virus Res, 143, (2009) 147-161. 2. O. Zhirnov. Virology, 186, (1992) 324-330. 3. M. Bu et al. J. Virology, 70, (1996) 8391-8401 4. E. Shtykova et al. PLoS One, 8, (2013) e82431.