The conformation of influenza virus haemagglutinin

Abstract

Received 1 June 1977 1. Introduction The haemagglutinin of influenza virus is the major glycoprotein of the virus membrane [ 1,2]. It is responsible for the attachment of the virus to the plasma membrane of the cell to be infected [3] and in an additional as yet undefined manner in initiating infec- tion [4,5]. In infectious virus particles the glycoprotein appears to be a trimer of molecular weight about 210 000 in which each monomer consists of two disulphide linked polypeptides HA1 and HA2 [6-81. During replication these are formed as the result of proteolytic cleavage of a precursor polypeptide (HA,,) of molecular weight about 70 000 which is the translation product of a single virus gene. Recently this cleavage has been shown to be essential for the formation of infectious virus particles even though in its absence particles which can bind to cells can be assembled. In addition these non-infectious particles containing HA,, can be activated in vitro by digestion with trypsin and concomitant generation of HA1 and HA2 [4,5]. The protein may be isolated following dissociation of virus particles with detergents [9] or by digesting them with the protease bromelain [lo]. The bromelain released protein (BHA) is soluble in the absence of detergent and lacks the hydrophobic region of the intact molecule which is associated with the lipid bilayer of the virus particle, As a result it is more amenable to physical studies aimed at elucidating its conformation than the detergent solubilized intact molecule (HA). Wiley and Skehel [ 111 have recently reported the initial results of an X-ray diffraction study of BHA crystals. In this communication the circular dichroism (CD) spectra of HAo, HA and BHA are presented. Since such spectra are sensitive to conformational changes in the protein molecules