User talk:Eman AlaliSandbox 1: Difference between revisions

(H) protein is the most important glycoprotein found on the virus surface for that it is responsible for the attachment of the influenza to the cells containing sialic acid receptors, such as cells in the upper respiratory tract. It also helps with the fusion between the viral lipid membrane and the host cell endosomal membrane (Shors, 2013). The H protein is a transmembrane protein consisting of two polypeptides, H1 and H2, which are linked by a disulfide bond between two cysteines. Full length protein is referred to as H0 (Shors, 2013).The H0 protein is homotrimer protein consists of three identical polypeptide chains, each polypeptide is 550 amino acids long that get glycosylated then cleaved into two chains (H1,H2) by the removal of arginine 329 along with a conformational change. <scene name='SAndbox_159/Ha1/1'>H1</scene> and <scene name='SAndbox_159/Ha2/2'>H2</scene> chains are covalently attached by a <scene name='SAndbox_159/Disulfide_bond/2'>disulfide bond</scene> to from one monomer. The one monomer noncovalently associates with two additional monomers to form one hemagglutinin homotrimer molecule (Proteopedia, 2015).

The H1 subunit consist of 328 amino acid composing eight stranded beta-sheet associated with little alpha-helix (Proteopedia, 2015). The H1 portion forms a globular bulb at the top of the structure and contains the sialic acid binding site. The amino acid of the alpha helix and some other beta sheets compose the binding pocket of the sialic acid subunit, and determine the attachment specificity of the virus to the host cell.

The H2 portion of H0 is called membrane-spanning anchor and it is directly involved in the fusion mechanism. H2 has a hairpin structure composed by two antiparallel alpha-helices. The C- terminal of H2 is embedded in the viral membrane while the N-terminal end contains 10 hydrophobic amino acid forming the fusion peptide (Proteopedia, 2011).

When H protein attaches to sialic acid residues of the ciliated columnar epithelial cell lining the sinuses and airways, the bound virus is endocytosed by the cell and the virions enter the cell within the endosomal vesicle. Then the endosomal vesicle  pH level drops and reaches about 5.5 due to the pumping of protons inside the vesicle by the M2 ions channel. As a result,  the H1 protein shifts its position, allowing the H2 protein to become embedded in the host cell membrane. Additionally, the C-terminus embedded in the viral membrane rearranges, bringing the two membranes closer together and facilitation fusion (Wilson et. al 1981). The pH induced conformational changes are partially but not completely reversible. As the pH decrease to 5.5,  the three globular heads start to dissociate due to the protonation of relevant H protein residues. the change in pH facilitate the releasing of the fusion peptides. Also at low pH the short and long alpha-helix are separated(Thoennes et.al 2008). The shifting of  H1 subunit plays an important role in H mediated membrane fusion , H1 protein helps the membrane attachment and fusion, which results in the release of viral RNA’s into the cytoplasm and then into the cell’s nucleus for RNA replication (Racanilllo, 2009).