| 학회 | 한국고분자학회 |
| 학술대회 | 2005년 봄 (04/14 ~ 04/15, 전경련회관) |
| 권호 | 30권 1호, p.469 |
| 발표분야 | 의료용 고분자 부문위원회 |
| 제목 | The origin of pH-dependent fusion activity of influenza virus hemagglutinin |
| 초록 | A low pH condition induces a large conformational change in influenza virus hemagglutinin (HA), which enables the virus to fuse with the target membrane. Recently, it has been observed that the fusogenic segment of HA can adopt the fusogenic conformation even at neutral pH1. This observation provides further evidence for the metastable model of native HA, implying that a decrease in pH can lower the kinetic barrier that prevents the native HA from adopting a more stable, fusogenic conformation. However, the exact nature of kinetic barrier, in particular, the effect of pH on the kinetic barrier is not clearly understood. In this study, first, as a possible factor for the kinetic barrier, the molecular interaction between a receptor-binding chain (HA1) and a fusogenic chain (HA2) is investigated in atomic resolution. Then, to investigate the effect of HA1 on the pH-induced conformational change of HA2 we have calculated the electrostatic free energy of HA2 as a function of pH in the presence and in the absence of HA1. It is revealed that there is a strong interaction between hydrophobic residues of HA1 and HA2 and hence the change of pH can hardly affect the interaction between HA1 and HA2, and that a lower pH enhances the pH-induced conformational change of HA2 from native state to fusogenic state irrespective of the presence of HA1. Therefore, it is likely that HA1 is directed away from the fusion site at low pH by the conformational change of HA2, not by the weakened interaction between HA1 and HA2 at low pH. In conclusion, although at neural pH the gain of free energy upon the conformational change of HA2 is not sufficient to overcome the strong hydrophobic interaction between HA1 and HA2, the difference of free energy between native and fusogenic states becomes greater at acidic pH for HA2 to overcome the strong hydrophobic interaction and displace HA1 from the fusion site and finally obtain the fusogenic conformation. 1. Swalley, S. E., Baker, B. M., Calder, L. J., Harrison, S. C., Skehel, J. J. & Wiley, D. C. (2004) Full-length influenza hemagglutinin HA2 refolds into the trimeric low-pH-induced conformation. Biochemistry 43, 5902-5911. |
| 저자 | 최호섭, 허준, 조원호 |
| 소속 | 서울대 |
| 키워드 | influenza virus; hemagglutinin; membrane fusion |
